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When Esther and Dan Levy’s son Andrew was 14 months old, he received a diagnosis of a kind of leukemia so rare that their medical team said getting it was like being bitten by a shark and struck by lightning at the same time.

Leukemia, a cancer of those cells in the bone marrow that produce new blood cells, has many varieties, but the most common type in children, acute lymphocytic leukemia, is largely curable. Andrew’s cancer, however, a subtype of acute megakaryoblastic leukemia (AMKL), affects only about 45 children a year nationwide and is much more difficult to treat. The odds of surviving this type of AMKL are roughly even — unless the child is one of a handful who happen to have a particular genotype, in which case these odds plummet to a mere one in 10. Genetic analysis revealed that Andrew was in this tiny group.

There was more bad news. Two weeks after the diagnosis, Andrew’s doctor, Norman Lacayo, an oncologist at Lucile Packard Children’s Hospital at Stanford University, received an urgent call from Michael Loken, the president of Hematologics Inc., a Seattle lab that was analyzing Andrew’s cells. Loken had recently discovered that a small percentage of children with AMKL had a specific phenotype — a pattern of proteins on the surface of the leukemia cell he called R.A.M. (a former patient’s initials) — that independently predicted a terrible outcome, with a survival rate of about one in six. Andrew had this phenotype too.

“Has anyone ever survived this kind of cancer?” Dan asked Lacayo. “All I wanted to know is that it was not impossible,” Dan recalls. Lacayo said yes, but Dan felt his answer was “foggy.” The truth was that the team couldn’t find a single equivalent case in the literature.

Beginning on that December morning in 2014 when Esther took Andrew to the E.R., she recalls, she felt as if they had stepped into a horror movie, the unfolding events both surreal and evil. Up to that point, Esther and Dan had led, in her words, “charmed lives — picture perfect.” Only a small subset of people would sincerely say that nothing truly bad has ever happened to them; before the diagnosis, Esther and Dan say, they were among them. When Andrew got sick, they were in their mid-30s and energetic, optimistic and extroverted. They had both attended Stanford — Dan majored in industrial engineering, Esther in human biology, with a minor in dance — before going on to successful careers. Dan founded a sports-related start-up, then became vice president of small business at Facebook, while Esther worked at Kurbo, a start-up focused on weight management for kids, and taught spin classes at a Jewish community center for fun. Their own families were stable and close-knit; to recall any true adversity in either family, they had to think back to a grandmother of Dan’s whose family perished in the Holocaust.

Once Andrew’s illness was diagnosed, he needed a bone-marrow transplant as swiftly as possible. First the doctors had to kill the leukemic cells in Andrew’s bone marrow with chemotherapy, then replace them with a donor’s cells. Andrew’s 3-year-old sister, Lea, and his 5-year-old brother, Wills, were tested, and in the family’s first bit of luck since the diagnosis, Wills turned out to be a perfect donor match. Andrew underwent two rounds of chemotherapy, but there were still traces of cancer when the transplant was performed in February 2015, putting the outcome at high risk of failure.

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The Levys had created a Lotsa Helping Hands website, where friends signed up to host play dates or deliver meals (as did our family because our children were in the same school as Wills), and a Facebook group for updates on Andrew’s illness, which 1,700 people joined. But despite all the support, Esther felt deeply “alone with the experience,” she says. Her former life had vanished: She was living in Andrew’s hospital room, sleeping on a sofa that opened into a hard bed. She had left her job and the rest of her family while Dan continued to work and live at home with Wills and Lea. Her nights were punctured by Andrew’s cries; her days were spent frantically trying to distract him from his pain and nausea, cleaning up his vomit, holding him down during blood draws and making stressful medical decisions. He screamed if she left him for a few minutes, even to use the bathroom or shower.

After Esther and Andrew spent three months in the hospital, the entire family moved into a nearby apartment, in order to live in a smaller space they could keep immaculately clean while waiting for Andrew’s new immune system to develop. Esther remained Andrew’s full-time nurse, responsible for a dizzyingly complex regimen of medications and sterile changes of the IV. A bone-marrow test that April showed no traces of cancer, and Andrew was considered to be in remission. They posted videos of him banging on his drums and singing with his toy Elmo and pretending to play golf.

They decided that when Andrew was well enough, they would not return to their old home but begin a new life. They found a house in the nearby town of Atherton in the style of an English country manor, encircled by hedges and white rose bushes, that suggested privacy and safety. Andrew was too vulnerable to leave the apartment, so Esther could not go to see the house in person, but they bought it anyway, and she made plans with a decorator friend to create an airplane-themed room for Andrew.

But on June 19, the medical team told Esther and Dan that there was bad news again: Andrew’s cancer had returned. The number of cells was small but would inevitably grow, the doctors explained. The team presented a new plan: They would begin chemotherapy again in preparation for a second bone-marrow transplant, perhaps using cord blood this time.

“Oh, God,” Esther said, putting her head in her hands. She felt she could not go through it all again. And there was no reason to think it would work. The odds of success during the first transplant had been long; in a second attempt, they would be much more so. “But the odds that it would cause all of us more suffering were 100 percent,” she told me.

From the initial diagnosis, Dan had determined that their goal was not simply to help Andrew survive but to keep the family intact. To choose to move back into the hospital, where they believed Andrew would die, was “a fundamental violation of every promise we made to ourselves and our kids that we would be together again,” he told me. He felt the family had just started to heal from the months of separation. “The emotional scars of the experience,” he said, “would be irreparable if we ripped them open and split our family apart again.” They decided to stop treatment. They would move to their new house, where Andrew would spend whatever time he had splashing in their swimming pool and playing in the grass with Wills and Lea.

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The doctors were stunned. “We love you, and we love Andrew and we’re not ready to give up,” Jennifer Willert, the pediatric oncologist in charge of the transplant, blurted out. Lacayo and Willert argued for at least trying some palliative chemotherapy to prolong Andrew’s life. Esther and Dan hesitated but ultimately declined. They called their decorator friend and told her to return the furniture for Andrew’s new room. She was one of the first people to whom they told the news: Andrew was going to die.

The Levys posted the news of their decision on June 22. They explained their thinking and asked their friends not to question their choices, recommend new treatment options, tell them about God’s plan or insist that there was hope. “I truly believe that I have a new way of looking at parenting — it is not about the length of life that matters, but the quality of life,” Esther wrote. “We are going to focus on quality.”

But quality time with a doomed child turned out to be impossible. The cancer cells were few enough that they were not yet making Andrew sick, but, Esther posted, “I can’t think of anything more painful than spending time with your precious baby knowing that he is going to die soon.” Parenting is teleological; parents rear a child to become an adult. What were their goals for Andrew now? “I am no longer ‘raising’ him to grow up to be a wonderful human being,” Esther wrote. Should she let him eat junk food or watch videos on the iPad all day? Did it matter?

Their older kids asked tormenting questions. Lea wanted to know whether they could buy Andrew a certain toy when he was 4 years old like her. Wills wanted to know why they had Andrew if they knew he was going to be sick all the time.

Dan read them Mo Willems’s book “Waiting Is Not Easy!” about an impatient elephant. As he read, he thought about the waiting that had engulfed them over the previous nine months. They had waited to get the right diagnosis; they had waited 100 days for the transplanted cells to grow; they had waited for the results from the bone-marrow tests to see if the cancer was gone. “Now there are no more diagnoses,” Dan wrote on Facebook. “No more tests. And no more milestones. But there is waiting. Maybe hours, or days, or weeks.” This was the most agonizing of all: the wait for Andrew’s death.

On July 1, they moved into their new house, and Andrew became sick. By the holiday weekend, he was moaning or screaming in pain whenever he was awake. Dan took a leave of absence from work. Esther held Andrew at all times, his body draped over hers on the couch or the bed. Dan took food to her because she couldn’t hold him and sit up at the dinner table. Her hair began to fall out because of the stress. “It was unbearable for him and for us,” she says.

The hospice team began to come every day to try to control the pain with high doses of opioids. Harvey Cohen, an oncologist and the medical director of the hospital’s palliative-care program, explained to them that as the disease progressed, Andrew would not have enough platelets for his blood to clot. A hospice nurse told them to buy dark towels for Andrew’s crib, so that if he started to bleed uncontrollably, the sight would be less frightening for his siblings and for them.

During the second week of July, the hospice team told them to prepare for Andrew’s imminent death. They called a rabbi, and thinking about how Andrew loved airplanes, they picked a Jewish cemetery near the airport. Not wanting him to be buried alone, they purchased grave sites for themselves as well. They established an Andrew Levy Memorial Fund to raise money for music therapy at the Lucile Packard Children’s Hospital.

The members of their medical team visited their home to say goodbye. Andrew had stopped eating. He was barely moving, his breathing raspy and his complexion sallow, with the particular look the team knew from other dying children. Sometimes he stopped breathing momentarily, and his body would become rigid, and his face turn blue. “It’s O.K. for you to go,” Esther told him. All she wanted now was for this to end quickly.

They called Wills and Lea into the living room — a room the kids rarely entered. Esther pulled them close to her on the couch, and Dan sat on a cushion on the floor. They had rehearsed what they were going to say with Barbara Sourkes, a hospital psychiatrist with whom they had grown close, and they made an audio recording of this moment in case they needed to discuss it with her later.

Dan told the children that the transplant had been a success, and that Wills’s cells had done a great job, but that Andrew’s cells needed to work on their own at some point, and they weren’t. “His body is just not working,” he said, as straightforwardly as he could manage.

“Is Andrew going to get better?” Wills asked.

“The doctors don’t think so, Wills. No.”

Sourkes had advised them to tell the children only what they needed to know so as not to overwhelm them, because the children needed emotional space to process things their own way. “So Andrew — Andrew is going to die at some point,” Dan said. “We don’t know when.”

“I don’t like that Andrew is going to die!” Lea exclaimed and started crying.

Wills pulled the hood of his sweatshirt over his face and said he didn’t want to talk about it.

“Andrew is going to die, so that means we are only going to have four people in our family,” Lea said unhappily. She asked if they could get a new baby to replace Andrew, and she and Wills began to fantasize about a new baby who would make everything all better.

Esther returned to Andrew. “I promise, I promise you, we are not going to forget him,” she said. “You are always going to have a brother named Andrew because he is always your brother, now and forever.”

“Andrew’s pieces of love will always be in our heart,” Lea said, and then they all agreed to watch Mickey Mouse together.

The vigil stretched on through the summer, and what they called “mirages” began to appear. In late July, Esther was sitting outside with Barbara Sourkes, holding Andrew and watching Wills shoot baskets. Suddenly Andrew sat up and reached for a ball and managed to throw it through his own little basketball hoop. Esther and Barbara were speechless.

At first the mirages were brief — Andrew would laugh when Lea showed him her bellybutton or would stack blocks for 10 minutes — and then he would lapse back into pained lethargy for the rest of the day. But soon these episodes began to lengthen. For Esther, the mirages did not feel like miracles but “evil tricks.” She went through intense surges of anger. “I felt like, How many trials are we going to have to endure?” she says. “Are we being spared nothing?”

Esther started sending the medical team videos. “Andrew is eating pizza, Andrew is sitting up, Andrew is laughing,” Lacayo, their oncologist, recounts. “And we are like, What?”

In August, as the team struggled to account for what was happening, they theorized that in July, when everyone assumed Andrew was dying of cancer, he must have had a terrible infection instead, which passed. It didn’t change the prognosis: The doctors stressed that, while Andrew might continue to recover from that infection as his new immune system took hold, the cancer cells were also growing and would eventually overwhelm him.

After a blood test showed that his platelets were low, Cohen, the palliative-care doctor, urged them to accept transfusions to increase Andrew’s platelets so that, even though he was going to die, it would not be from bleeding to death. But at the hospital, it turned out, mysteriously, that Andrew had more platelets than at his last blood test, so there was no need for a transfusion that day. When Dan suggested giving him vitamins, Esther snapped at him. He seemed to be taking the anomalous blood test to mean Andrew was getting better, when, she says, “I had no hope, and I needed not to have hope in order to function.” And then they both apologized.

In September, Andrew began to walk again, and his appetite and energy and dark curls grew. Dan decided to return to work. Andrew turned 2 — a birthday his parents had never thought he would reach and knew would be his last. Esther recalls how friends urged them to enjoy every moment, and how she would tell them: “No, this is hell, and it sucks. He is still going to die, so there is nothing joyous about this time.”

When they first got Andrew’s diagnosis, she told a night nurse that she just wanted to get her happy-go-lucky little boy back for a single hour. She had not understood then that any reprieve would only mean that they would have to go through losing him all over again — “and each return will be harder than the last as Andrew grows and bonds with us,” she wrote in a post.

By October, Andrew was healthier than he had been in a year, running and playing ball with his siblings. None of the doctors had ever seen this kind of recovery before. They decided to bring him back to the hospital for a bone-marrow test.

Michael Loken, who had analyzed Andrew’s blood work, had not been surprised that Andrew’s cancer returned. He had been working on a paper about R.A.M., the genetic marker that Andrew had. He had tracked 19 other cases of children with the phenotype; three years after the diagnosis, only two were still alive and healthy. When he examined Andrew’s marrow this time, using a sample of 200,000 cells, he got goose bumps. He repeated the test with 500,000 cells. Then he called Lacayo with the news. The cancer had disappeared.

How could cancer spontaneously disappear? “It does feel a bit like a miracle,” says Jennifer Willert, the transplant doctor, echoing the sentiments of others. Noting the rare evocation of a concept that stands outside science, Loken says: “It certainly defied our expectations with no discernible basis of happening. I guess this may be the definition of a miracle.”

The medical team grasped for a scientific explanation. Because Andrew had received no treatment over the summer, the answer had to lie in the bone-marrow transplant of Wills’s cells. Their main theory was that the infection that nearly killed Andrew in July had triggered a huge increase in his new white blood cells — and that heightened immune response had attacked not only the infection but the cancer cells as well.

The doctors theorized that the response was partly a product of timing: The cancer had returned just as Andrew’s new immune system grew strong enough to destroy the cancer cells. A critical part of why transplants work is that some of the white blood cells, the T cells, that grow from the transplanted bone marrow will attack any lingering cancer cells, an effect known as graft versus leukemia. Chemotherapy rarely kills every last cancer cell, so it is believed that without graft versus leukemia, the cancer will eventually grow back. This is often spoken of as a model of so-called immunotherapy — stimulating the patient’s own immune system to attack cancer cells — which is widely regarded as one of the most promising avenues for cancer treatment.

Willert had made a key decision to depart from Stanford’s protocol to increase Andrew’s chances of getting a robust graft versus leukemia effect. Typically, a leukemia patient receives immune-suppressing drugs for at least 100 days (and often much longer) in order to avoid a serious side effect called graft versus host disease, in which new T cells attack not only the cancer cells but also the patient’s skin, liver and gastrointestinal tract. The art of a transplant is said to be maximizing graft versus leukemia while minimizing graft versus host.

Willert, who is now at the University of California, San Francisco, Benioff Children’s Hospital, had advocated a rapid early taper of Andrew’s immune-suppressing drugs on Day 60, as is the practice at U.C.S.F. and other places, because she felt that the benefits outweighed the risk of graft versus host. “I fought for it because I have seen the power of getting rid of immune suppressants and letting the cells do their job,” she says. “After all, that’s the whole point of a transplant!”

The final, critical decision was made against medical advice: Esther and Dan’s resolution to stop treatment and let Andrew die. Had they permitted more chemotherapy, the treatment would have killed Wills’s cells, which were what ultimately enabled Andrew to live.

“When you have a child with a life-threatening illness, you have an irrevocably altered existence,” Barbara Sourkes had told the Levys, and Esther feels that is true. She had always felt in control of her fate, but now she believes this to be a fiction. She finds it difficult to reconcile bitterness over the blight of Andrew’s illness with gratitude for the reprieve. “We are the luckiest of the unluckiest people in the world,” she says. “I truly believe that.” The story presents itself to her as a riddle that cannot be resolved. She recalls her anger when others told them to hope. Is the lesson that their friends were right and there is always hope? Yet it was only by letting go of hope and accepting Andrew’s death that he lived.

She has not returned to work. “My full-time job is to help the kids feel safe again,” she says. But it is hard for her to feel safe. The two years after a transplant are the riskiest time for a relapse; after two years that likelihood plummets, and after five years, a patient is considered cured. The two-year mark is still nine months away.

“There are only two states after such a diagnosis: disease and uncertainty,” Cohen had told them. “Either he will die soon, and that’s certain — or he will continue on, and you will live with that constant balance of hope and fear. But the balance will change as time goes on.”

Only in the past few weeks, Esther says, has she been able to feel that she isn’t testing fate by scheduling a dentist appointment for Andrew six months out or by feeling moments of joy watching him without being shadowed by fear of the future. “Day by day,” she says, “we are allowing ourselves to celebrate a little more.”

Correction: May 29, 2016

An article on May 15 about a child with a rare form of leukemia gave an incomplete name for the website that the child’s parents used to arrange play dates and meal deliveries. It is Lotsa Helping Hands, not Helping Hands.

Who wouldn’t be wanting to have a drug that may help battle age-related disease, to confer extra many years of a proper existence?

Actually, many readers in our article about rapamycin claimed they’d just avoid this type of drug. Rapamycin was tested throughout a study of dogs in the College of Washington to find out if it might slow aging without a lot of harsh negative effects.

Lisa Wesel of Maine spoke for those who contended that attempting to extend existence was like playing God.

“This is disturbing on a lot of levels,” she stated. “You can’t cheat dying. Period. Nor in the event you try. Live a great existence. Live a good existence. That needs to be the aim. The planet cannot sustain billions and billions of people that possess the arrogance to think the world is much better served by them than without one.Inches

Librarian, writing from California, felt similarly.

“Old age, sickness and dying, however frightening and alarming they might be to everyone once we consider our very own fates, would be the natural order of products,Inches she authored. “Why will we spend a lot time, money and angst battling the inevitable rather of accepting with elegance the program that lives will need to take? Obviously we don’t want to be sick and miserable and suffer discomfort and indignity, but individuals fears have brought us to appear on dying as some type of cruel, almost shameful, obscenity that people must resist and deny, very frequently with treatments which are by themselves terrifying and horrifying.”

Others expressed worry about the ecological and economic implications of the longer life time.

“Ah, the unintended effects of extending existence — overpopulation, growing force on a previously stressed atmosphere, growing force on a previously stressed retirement system,” authored Thomas G. Cruz, in Cadillac, Mi. “Humans would be the most destructive of species, and also the rate of the world degrading is constantly on the accelerate through the envy people. I’ve been a household physician for 32 many curently have seen the modification introduced on by existence extension of just ten years. We’ll need strict policies to combat the side effects of existence extension of 3 decades.Inches

One readers acknowledged the appeal of having the ability to experience with one’s great-great-grandchildren. “But how in blazes shall we be held supposed so that you can manage to live that lengthy?” requested FJP in Philadelphia. “If the reply is I would need to try to age 85 in order to make it to 120 or beyond, I am not sure I’m going to enroll in that.”

Still, numerous readers found the research intriguing.

“I’m unsure the way i experience the thought of a medication to create people live longer, but I’m undecided about all of the comments against it,” Al Maki from Burnaby, Bc, stated. “I’m 66, and that i get some exercise regularly and learn my diet with the hope which i will live longer and healthier. Lots of people do that and many more wish they’d the self-discipline. I’m surprised a lot of people think this can be a selfish goal. It’s appears really common in my experience.Inches

Patrick, from Chicago, agreed: “Why, oh why, a multitude of people commenting that we’re in some way ‘meant’ to reside a finite life time, and now we must cope with it, and never try to look for methods to extend our existence? I only say that’s absurd. I like my existence, and when I possibly could come with an extra couple decades, where I’d eat well, I’d be thrilled. So, I believe, would most of the naysaying commenters, if really because of the option.”

Another readers place the current research into historic context.

“It’s not about living forever,” David Bird from Victoria, Bc, described. “It’s in regards to a holistic method of coping with age-related illnesses, for example Alzheimer’s and lots of cancers. For individuals who dismiss or condemn it, existence expectancy, at birth, for any white-colored American male rose from 47 to 75 from 1900 to 2000. For black males it rose from 33 to 68. You do not think this really is abnormal since it is our norm, however it wasn’t standard for the great-grandma and grandpa. When the results found for that rodents might be replicated in humans, we’d live only 12 % longer, under ten years, but our last years could be healthier, putting significantly less stress on ourselves, our families, and our medical sources.”

Wendy from Wyoming added: “I work very carefully with people who are attempting to navigate the Social Security disability process, the majority of whom are 45-64 years of age. During the most efficient duration of their financial lives, they’re literally impoverished by illnesses of early aging — early cardiovascular disease, advanced osteo arthritis, early cancer. … I strongly support any treatment which keeps people productive and from assisted living facilities until their 80s and 90s. Everybody discusses ‘the nature of getting older,’ but among the facts concerning the human condition is the fact that we already cheated nature many occasions over our transformative development. The very first hack happened once the human species could get old enough to deliver valuable survival information from grandparent to grandchild, which corresponded to some dramatic improvement in human survival.”

Possibly probably the most passionate voices, though, originated from readers completely unconcerned about human life time.

“Not sure I wish to live forever, but my dog? YES!” announced John from Montana.

“I shouldn’t live longer, but when dogs could live longer that might be wonderful,” a readers named Mary mused. “Beloved dogs are extremely soon gone from your lives.”

“The heck with human research — Among the finest my dogs to reside longer,” Durt from La stated.

A readers whose dog was one of the 40 studied chimed in. “My dog Rascal is featured within the article, and I’ve been thrilled using the outcomes of the medical trial,Inches Rose and Rascal authored from San antonio. “This drug made Rascal’s heartbeat more proficiently again enjoy it did as he would be a more youthful dog. He’s more happy and friendlier and it has more energy. Whether it buys me an additional couple of years with my big dog — who’ll not live as lengthy as smaller sized dogs — then I’ll go. One factor which didn’t allow it to be in to the article: Rascal is my service dog, like me disabled. … Rascal may be the passion for my existence, and that i have labored hard his entire existence to make sure he get top quality food, plenty of exercise, and rigorous training to create him the healthiest and most joyful dog he is able to be. … Through an assist from science nearly ten years later is really a BONUS.”

Finally, Concerned Citizen from Anywheresville gave voice towards the issues natural in prolonging either canine or human existence.

“I lost my dearest and many beloved ‘heart dog’ 4 years ago,” she described. “I loved her a lot, I’d did literally anything legal or safe to help keep her beside me a couple of more years. Basically had the sources, I’d have experienced her cloned. I had been nearly crazy with grief in the loss. But … if she’d not died, your dog I’ve now might have most likely died inside a shelter. Because it was, she was awaiting eight several weeks and not having enough time, on and on ‘kennel crazy.’ She was older, and overweight nobody wanted her. I wouldn’t have become another dog. Which means this dog might have died, had my other dog resided.”

She added: “See? it’s all a cycle which is all connected. Can there be meaning and purpose behind this? A great design? I suppose I won’t know myself before the finish.”

For years, Grace Silva had experienced odd episodes with her throat — bouts of swelling and radiating pain that seemed to resolve with antibiotics — but her doctors couldn’t explain what was wrong. Finally, after a flare-up in the summer of 2010, Grace was referred to a specialist, an ear doctor who felt something amiss on the left side of her throat: a lump. The Silva family agreed that it was time to get Grace, then 54, to a thyroid specialist. Grace’s daughter Melanie tracked down the name of one at Brigham and Women’s Hospital, a 90-­minute drive from Grace’s brown clapboard split-­level near New Bedford, Mass. In September 2010, the specialist delivered the diagnosis: anaplastic thyroid cancer. It was bad, he warned her, and she would need surgery. Grace’s other daughter, Karrie, was marrying in a few weeks. “Can’t it wait?” Grace asked. It could not. “And whatever you do,” the specialist said, “please don’t look it up on the Internet.”

Medical texts describe the prognosis for anaplastic thyroid cancer as “poor,” but that hardly captures it. If every cancer has a personality, this one is notoriously aggressive. Its tendrils of tissue are so invasive that by the time of diagnosis, it is often too late to operate safely. Radiation or chemotherapy rarely buy much time, and even when all traces of the tumor are eliminated, it usually reappears. Anaplastic thyroid tumors are also known for their aberrant firmness, more akin to wood than flesh. As they bloom, the tumors can tighten like a noose, constricting the windpipe and giving their victims a sensation of perpetual drowning. This panicky “air hunger” can be mitigated with escalating doses of morphine, but it’s a miserable, desperate end that, once witnessed, is not easily forgotten. The oncologist Grace was sent to, Dr. Jochen Lorch of the nearby Dana-­Farber Cancer Institute, had watched a patient die this way during medical school, and it filled him with such horror, such helplessness, that for years he felt sure he would never pursue a career in cancer treatment.

Of course nobody dreamed of saying these things to Grace at the time. A surgeon removed her tumor, and she was able to attend her daughter’s wedding. She then withstood a long stretch of radiation, every weekday for more than a month — vomiting into a bag as her husband, Joe, did his best behind the wheel of their brown Chrysler. Her doctors knew they had to hit the cancer with everything they had. By the end of her treatment in December 2010, Grace, a once-vivacious Portuguese woman with dark eyes and raven hair, had lost more than 30 pounds and could barely eat or talk.

In March 2011, Joe drove Grace back to Dana-­Farber. She had started to recover some of her strength, and the day had come to learn the results of her first follow-­up scan. The news wasn’t good. Less than three months since her last radiation treatment, the cancer had already spread to her lungs. The largest mass, on her right lung, was more than an inch in diameter. This is the way with anaplastic thyroid cancer.

Lorch sat with Grace and Joe in a cream-­colored exam room, a red biohazard box nestled under one counter, and explained that all the standard treatments had been exhausted. He told them about an experimental trial for aggressive thyroid cancers that hadn’t responded to standard treatments, and Grace agreed to enroll. The drug, everolimus, was used in transplant surgery to prevent rejection, and it had been approved for some use in cancer. Lorch had seen indications that the drug could work in the thyroid, but he didn’t have high hopes for the anaplastic cases — its long track record had been too dismal. “Partly we were motivated,” Lorch told me, “by the fact that we didn’t have anything else.”

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In the days after starting the trial, Grace found herself standing in front of the mirror in her bedroom, taking in her diminished reflection, beseeching God to give her some kind of sign. If her time had come, she wanted to know, for the sake of her husband and three children. “If I’m going to die, I need time to prepare,” she recalled thinking at the time. Either way, she felt sure that God would hold her by her “right hand,” as in one of her most cherished lines from the book of Isaiah.

Two months later, in May, Joe drove Grace to Dana-­Farber for her follow-­up scan. Lying motionless as the CT scanner began its inquiries, she thought of Isaiah and prayed. If the everolimus had failed to slow the cancer’s advance, it would be time to begin the work of getting her affairs in order. But the scan results, plain to even an untrained eye, were shocking: The largest mass had shrunk to half its previous size. Everywhere there were signs of retreat. Lorch said he had never seen such a rout. All six of the other anaplastic thyroid patients on the trial eventually died, but Grace’s tumors shrank until they barely registered.

Grace’s case became the subject of intense scientific scrutiny. How could such a notoriously recalcitrant cancer simply collapse? Why had she alone responded so extremely? Nobody was claiming that she was cured. But by the end of 2011, Grace felt this much was sure: Having asked for a sign, she had become a walking miracle.

What happened to Grace is sometimes called by another biblical name: the Lazarus effect, after the story in which Jesus stands outside the tomb of Lazarus of Bethany and summons him back to life. Many veteran oncologists have seen cases like Grace’s, and the stories of these unlikely recoveries, shared online or by word of mouth, have become a source of hope for patients. Yet for the field itself, the Lazarus effect has been a source of persistent frustration. In 2011, for example, the Food and Drug Administration withdrew its support for the treatment of breast cancer with Avastin, a drug with proven efficacy on tumors in other organs. Some breast-­cancer patients had experienced powerful responses — and owed their lives to the drug — but most patients weren’t helped and were instead exposed to unnecessary side effects. With no way to predict the results, the drug was as good as useless.

Today patients like Grace have come to be known as exceptional responders, and cancer researchers have finally begun to unravel the puzzles they pose. In a cancer, some of the body’s cells develop genetic aberrations, growing and spreading uncontrollably, and there are myriad variations on this theme. While physicians recognize hundreds of types of the disease, genetic analyses suggest that the true number is far higher. The closer that scientists look at tumors, the more mutations they find, to the point where it may be impossible to count the types of cancer. Really, every patient suffers her own personal cancer, and when a drug is perfectly aligned to it — to the exact set of mutations driving the tumor — the result is an exceptional response. In such a case, if scientists could catalog the tumor’s mutations, they would have a shot at reconstructing a play-by-play — how the conflagration began, how the drug smothered it — and, from this, gain insights that could help others.

The power of this approach was first demonstrated a few years ago, at Memorial Sloan Kettering Cancer Center in Manhattan. In April 2009, Sharon K., who was 68 at the time, had been told by her local doctor that her bladder cancer had morphed into a muscle-­invasive form: It had become aggressive and difficult to contain. At Sloan Kettering, she was given chemotherapy, followed by a cystectomy, which involved removing the bladder and fashioning a new one out of a portion of small intestine. “I felt like my insides were going to fall out,” said Sharon, who asked that her last name not be used to protect her privacy. Still, a few months later, the cancer returned.

In February 2010, running out of alternatives, Sharon joined a clinical trial at the center, with instructions to take two pills every morning and return for regular checkups. Thousands of trials are open in the United States on any given day, and for people like Sharon, who traveled from Florida to take part, they are an opportunity to take advantage of the latest scientific ideas. But the odds are generally long: Historically, less than 7 percent of cancer drugs tested in humans eventually win F.D.A. approval.

At Sharon’s first follow-­up scan, the tumors were in recession; within months, they were gone. Her doctors were thrilled. And yet the trial Sharon had joined was a failure. Of the 44 other patients, just one saw his tumor shrink in a meaningful way. Dr. David Solit, a researcher at Sloan Kettering, joined a meeting with his colleagues there to discuss the trial’s results, and he remembers the feeling in the room, familiar to anyone in the field. “O.K., we’ve had no new effective bladder cancer treatments for 30 years, and we did yet another clinical trial that was [based on] a reasonable idea,” he recalled. “This is a disappointment. Now let’s give up and move on to the next thing.”

But before they did, they wanted to look into Sharon’s exceptional response. In the previous few years, a new technique called next-generation sequencing had made reading an entire genetic code exponentially faster and cheaper. Curious to see what the technology was capable of, Solit and his colleagues sent Sharon’s tissue to Illumina, a sequencing company with headquarters in California. Three months later, Illumina sent back what amounted to two Human Genome Projects: a complete readout of her DNA, totaling some three billion base pairs of code, and then another, equally large, for her tumor. After months of investigation, considering the potential significance of the tumor’s various mutations, the researchers settled on a prime suspect, a gene called TSC1. When they re-­examined the failed clinical trial, they discovered that the bladder-cancer patients genetically similar to Sharon had done noticeably better, staying in the trial substantially longer. The problem hadn’t been the drug, but knowing exactly who should receive it.

When Sharon’s doctors published a paper on their findings in the journal Science, researchers at the National Cancer Institute in Bethesda, Md., immediately understood the broader implications. They sifted through a decade of “failed” clinical trials, thousands of cases, and found that more than 100 patients had experienced impressive positive effects. More Sharons were out there, each potentially harboring a secret about how to defeat cancer.

In 2014, the institute started the Exceptional Responders Initiative, and since then the case reports have come in, each a tantalizing mystery. What explains the patient with a Stage 4 esophageal cancer that spread to the liver but then disappeared three years ago? Or the Stage 4 adenocarcinoma patient who experienced a complete remission? What can we learn, from each Lazarus, about how to save the lives of others?

The first surviving record of treating cancer dates to around 1600 B.C., in an ancient Egyptian papyrus: tumors of the breast, excised and cauterized with what is described as a “fire drill.” In the centuries since, oncology has retained something of this elemental character. It is a bodily assault, brutal but necessary, guided largely by trial and error. The Boston hospital where Grace was treated takes its name from the cancer researcher Sidney Farber, who pioneered a treatment for childhood leukemia in the 1940s using aminopterin, a poison that racked his young charges but held the disease at bay, at least for a time. What works and what does not with one generation of patients is used to guide treatment for the next.

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Today, a better understanding of cancer’s workings is transforming treatment, as oncologists learn to attack tumors not according to their place of origin but by the mutations that drive them. The dream is to go much deeper, to give an oncologist a listing of all a tumor’s key mutations and their biological significance, making it possible to put aside the rough typology that currently reigns and understand each patient’s personal cancer. Every patient, in this future situation, could then be matched to the ideal treatment and, with luck, all responses would be exceptional.

This idea, more broadly, has been called precision medicine: the hope that doctors will be able to come to a far more exact understanding of each patient’s disease, informed by genetics, and treat it accordingly. It is in cancer where this has advanced the furthest, and the exceptional responders provide a glimpse of what precision medicine might mean. When Grace’s tumor was sequenced, scientists found a mutation in TSC2, a sister gene to TSC1, the one mutated in Sharon’s cancer. Sharon, like Grace, had responded to everolimus, and so the genetic similarity suggested that their cases were not flukes, that their seemingly different cancers shared a deep connection. In this sense, Grace’s anaplastic thyroid cancer more closely resembled Sharon’s bladder cancer than other thyroid cancers. A more precise oncology would have assigned both to everolimus on purpose, not by chance.

Still, the two women’s tumors were not identical: While Sharon’s cancer vanished, Grace’s still lingered, even if it was harder to discern. Grace’s disease barely showed on the scans, and she looked healthy; friends and family found themselves forgetting, from time to time, how seriously ill she was. Dr. Nikhil Wagle, a Dana-­Farber physician and scientist who worked on the genetic analysis of her tumor, was once involved in the case of a 38-year-old man with metastatic melanoma. A photo, taken when he joined a trial for the drug vemurafenib, shows the man’s chest, pale with a greenish cast, covered in large, oblong tumorous bumps. Cancer derives from the Greek for “crab,” and in this case, it was easy to see how the ancients imagined crab claws in cancer’s eruptions. After 15 weeks, though, another photo shows the man’s chest almost completely smooth, its healthy color restored. Lazarus, touched by vemurafenib. Then, two months later, the man’s chest is wan and bandaged, with protrusions so substantial that they are visible in profile at his neck. He died in hospice.

In June 2012, a year after Grace’s miraculous recovery, Maddox, the first of her three grandchildren, was born. The happy beginning of the next generation was all the more meaningful for Grace because she had not expected to witness it. But cancer doesn’t rest, and Grace’s doctors knew she faced the same threat as the man with metastatic melanoma. If a tumor cannot be eliminated, drug resistance is the rule. As the biological machinery goes awry inside a cancerous mass, reproducing cells make more errors copying their DNA, releasing a stream of mutants. The everolimus had made conditions harsh, but if a mutant should arise that could thrive despite the drug, it would divide, and divide again, eventually taking over and spreading. Darwin’s survival of the fittest governs inside a tumor, selecting for a crueler version of the disease. The cancer was looking for a new way out.

Grace is a pioneer, which means that others might learn from her. But it also means that her doctor, Jochen Lorch, has no precedents to guide him, because her case is without precedent. Within months of Maddox’s birth, he had to tell Grace that a substantial mass had appeared near her right lung and that several smaller nodules had taken root nearby. The tumor was “progressing” — surely one of medicine’s most perverse coinages.

When Grace became resistant to the everolimus, Lorch decided to try a pharmaceutical cousin, temsirolimus. (Resistant tumors sometimes stick to the same basic escape plan.) Lorch also asked if she would be willing to undergo a biopsy, so that the resistant tumor could be sequenced and compared with the original. This, he explained, might help future patients who faced everolimus resistance.

To understand that cancer is genetic is also to realize that the disease lurks within a biological system that has about 20,000 genes, each vulnerable in many ways. Some day, researchers hope to be able to develop a comprehensive resistance map for cancer, a full accounting of the ways that the disease, in all its varieties, defeats different therapies. The sequence of Grace’s resistant tumor could fill in one tiny part of such a map. Eventually, some scientists believe, treatments for most cancers could come in the form of multiple advanced therapeutics, applied in parallel. One would be aimed at containing the tumor’s current mutations, while the others would target its favorite backups. Hemmed in and blocked from shifting to Plans B or C or D, the insurrection would collapse.

When Lorch suggested the biopsy, Grace was preparing for her grandson Maddox’s dedication ceremony, and she knew that any surgical complications might put her attendance at risk. But her faith assured her that there was a reason she had happened into Lorch’s care — that any adversities she faced would eventually lead to a greater good. “She is deeply convinced that what we are doing here, and what is happening with her, is all part of a plan,” Lorch says.

At Maddox’s ceremony in November 2012, Grace’s ribs flared with every breath. The biopsy had gone smoothly, but the area was still tender. Grace used to be a standout in the choir, and one of her favorite hymns had always been “It Is Well With My Soul,” but since the radiation damaged her vocal cords, she had been unable to sing. A few months passed, and the temsirolimus wasn’t working. Lorch tried another drug; it didn’t work either.

One of the more grotesque insights yielded by cancer genetics is that many of the genes implicated in the disease are the same genes that guide early human development. All of us begin as a relatively formless embryo, and from there the cells follow an elaborate program. They grow rapidly. They migrate and specialize, taking on roles like nerve or skin or the production of hormones in the thyroid. Cells that are no longer needed die willingly. All of this activity is ordained in our DNA and orchestrated by an elaborate system of cellular communication in which genes activate and deactivate one another as needed. It is hard to imagine, but this cooperative dance is what allows an unshaped mass of cells to become something as perfect and graceful as a baby’s tiny hand, with each fingernail sculpted just so.

In Grace’s body, cancer hijacked this system and turned it to its own ends. For example, the gene that mutated in Grace’s original cancer, TSC2, is part of what’s called the mTOR pathway, which helps direct cellular growth. Normally the TSC2 gene acts as a brake, sending cease-­and-­desist orders to the mTOR gene when it’s time for the cellular engines to ease. The mutation trashed the brakes, locking the cells in overdrive. Everolimus, however, acts on the mTOR gene directly, limiting its ability to emit growth signals — an emergency brake. When Grace took it, her cancer faltered.

Early in 2013, Grace’s team received the sequence of her resistant tumor, and its trick was revealed: A single letter of DNA had changed in the mTOR gene. This solitary substitution meant that a lone amino acid, part of a long chain that makes up the mTOR protein, was different. Because of this, the mTOR protein assumed a slightly deformed shape, and this meant that the everolimus could no longer grab hold and do its work. The cancer roared to life. It sounds like truly extraordinary bad luck — a one-in-three-billion shot — but the power of evolution means that it’s entirely predictable: Inside the tumor, cancer rolls a pair of dice, over and over, until they come up snake eyes.

Often cancer appears to reverse the natural course of things, by taking mature cells, disciplined in form and function, and returning them to a more fevered, inchoate state. Anaplastic cancers like Grace’s are those in which the cells have lost their characteristic form. Seen on a pathology slide, normal thyroid follicular cells have a smooth, rounded look, like uncracked eggs, and they are arranged in neat circles. With anaplastic thyroid cancer, the cells swell up into a mess of irregular shapes, as if they’d all been melted together. They are reproducing so often that it’s not unusual for a pathology slide to show a cell in the middle of doubling, caught in the act.

Cancer is a monster, but in its fierce evolutionary tendencies, it is grasping, as with anything else in nature, for a way to be in the world. Life on earth has invaded the air, the deep sea, the bedrock. Over eons, it has suffered meteor storms, volcanic dystopias, shifting continents and deprivations beyond counting, and yet it always comes back stronger. With cancer, biology’s fierce insistence — its resilience, its ceaseless creativity, its sheer generative capacity — is the enemy. With cancer, the opponent is life.

As Lorch considered other ways to help Grace, he knew that one option might come from the pharmaceutical company Millennium, in Cambridge, Mass., which was working on a next-­generation mTOR inhibitor, a drug that, like everolimus, targets the mTOR gene. By the summer of 2013, Wagle’s colleagues at the Broad Institute of M.I.T. and Harvard, where he has a position, had made some progress. After creating a proxy cancer, a collection of cells with the specific mutation found in Grace’s resistant tumor, they applied a compound that mimicked the activity of the drug by Millennium, which is now called Takeda Oncology. The drug should work, they concluded. The company told Lorch that it would support a clinical trial as soon as the drug was ready. Grace had agreed to the biopsy to help future patients, and now she had a chance to become one of them.

For Lorch, the challenge was to keep Grace alive long enough to join the trial. He knew her tumor was always in motion. Under the long press of everolimus, it had mutated, allowing it to resurge. The tumor then shook off two other drugs, including temsirolimus. Lorch decided to go with a traditional chemotherapy combination: carboplatin plus paclitaxel. In July 2013, he started Grace on the new therapy. As fall arrived, hair was slipping from her scalp, but the cancer had gone quiet, pharmaceutically stunned.

For all the excitement surrounding precision medicine, it is humbling to see how distant a goal it remains, even in cancer. There was nothing especially precise about the chemotherapy Lorch prescribed for Grace, and this, for most patients, is the reality today. Despite all of oncology’s recent successes, our understanding of the human cell’s vast genetic machinery — cancer’s playground — remains modest. The original Illumina sequence of Sharon’s tumor revealed a total of 17,136 mutations. Pick any one and inquire about its significance, and the answer will most likely be: Who knows?

To make the shift to precision oncology, cancer researchers have invented a novel means to evaluate new treatments. Called a basket trial, it is a trial for which patients are recruited by the tumor’s genetic signature, not its point of origin in the body; a drug is thus tested against a basket of many cancer types. Last August, an international team led by researchers at Sloan Kettering published some of the first results of such a trial, for cancers with a mutation in a gene called BRAF. The doctors saw a good response in lung cancer and two rare cancers, showing the power of selecting drugs based on tumor genetics. For other cancer types in the trial, though, the drug was less effective, or there were too few patients to draw conclusions, showing how much more remains to be learned. Sometimes targeting a mutation fails because it is only one of many driving the tumor, or because the mutation occurred at random in the genetic chaos, a passenger, while other mutations do the driving. Future basket trials could help doctors tease out the distinctions.

Many such trials are now underway, including a large federally supported effort called NCI-Match. Sharon and Grace’s cases even helped inspire an everolimus basket trial. Carole Arenson, an 80-year-old Illinois woman, has metastatic sarcoma with a mutation in TSC2, the same troublesome gene implicated in Grace’s disease. Carole joined the everolimus basket trial and, in November, she learned that the tumors were shrinking. In this, the scientific investigations can be seen coming full circle, from a pair of Lazarus miracles to practical medicine that, to Carole, has felt like salvation.

When I met Lorch in his office last year, he was optimistic. Grace had just started on the Takeda Oncology drug, and the initial signs pointed to considerable shrinkage. Back in the fall of 2010, when she first received her diagnosis, her life expectancy could be measured in months. “We are trying to turn [cancer] into a chronic disease,” Lorch said. “Right now, to have someone still alive five years after they were diagnosed and enjoying her grandkids is the best that we can do.” As we spoke, though, on his computer screen was a scan with spots: masses of Grace’s tumor cells, within which, concealed from him, the cancer was surely plotting its next escape. Lorch sat a bit sideways on his chair, leaning back with his hand a loose fist on his forehead, as if he were bracing for impact. “When her time comes, it is going to be hard to speak with her husband and all the people who’ve come in with her over the years.” He paused. “Am I dreading this? Yes. Does it motivate me to try harder to keep her around? Yes, absolutely.”

President Obama’s $202 million Precision Medicine Initiative, announced during his 2015 State of the Union address, seeks to study one million American volunteers to learn how genetic and other data might be used to tailor treatments. The initiative aims for progress in many ailments, including heart disease, diabetes, obesity and depression, but initially the focus is cancer. In January, in his final State of the Union address, Obama announced that he was putting Vice President Joseph R. Biden Jr. in charge of a “moonshot” to cure cancer. Beau Biden, the vice president’s son, died in May 2015, at age 46, of brain cancer. The president’s mother died of uterine and ovarian cancer. “For the loved ones we’ve all lost,” Obama said before the joint session of Congress, “for the families that we can still save, let’s make America the country that cures cancer once and for all.”

Two days after the president’s moonshot speech, I was on the eighth floor of the Charles A. Dana Building in Boston to visit Wagle at Dana-­Farber. Last October, Wagle unveiled the Metastatic Breast Cancer Project, inspired partly by his involvement in Grace’s case and partly by frustration over the way cancer research works today. It’s quite difficult to track down patients with intriguing case histories, scattered as they are across the country and protected by blankets of privacy. So instead of going through doctors or hospitals, the project makes its appeal to patients directly. Through the project’s website, they can enter their medical histories and grant Wagle’s team access to their records, their DNA and tumor samples. Participants have started recruiting others to the project, solving a central challenge facing the scientific study of any rare phenomenon. In six months, more than 1,800 patients with metastatic breast cancer have joined, including hundreds of exceptional responders. In return, the project involves them in its decision-­making and promises to share its data with any scientist who asks. “A lot of patients feel like the research-­industrial complex is about making discoveries and competing for grants, and in many ways they are right,” Wagle said. “I get it.”

The project cuts against the grain of a medical system that was not designed to learn from patients. Every day in this country, doctors treat people for all kinds of disorders, and some do surprisingly well, or surprisingly poorly — and virtually all of this information is lost to science. Eric Lander, the founding director of the Broad Institute and co-­chairman of the President’s Council of Advisors on Science and Technology, has begun laying the groundwork for a national project he calls Count Me In, which would allow anyone to make their medical records, and DNA, available to researchers. “In my opinion,” Lander said, “it’s a crime to let valuable information go to waste when a patient wants to share it.”

Wagle’s project is Count Me In’s first undertaking. Next, Count Me In is beginning a similar effort on angiosarcoma, an understudied cancer, and two more efforts are planned this year. Precision oncology has been driven by advances in two areas: automation, responsible for the plummeting cost of genetic sequencing, and information technology, which allows the data to be recorded and interpreted. Projects like Count Me In are built on the premise that a third disruptive technology can also be brought to bear: social media.

The campaign by American political leaders to cure cancer goes back decades, including Nixon’s “war on cancer.” But these latest federal calls for action — which bring to mind images of the best and brightest, backed by brute force — risk mistaking the nature of the opponent and misunderstanding the potential of the weapons now available. Ask almost any specialist about a cure for cancer, and she will cringe, because there is no one cancer to be cured. We face an enemy that is resourceful, changeable and merciless, but we have a population that wants to help. Instead of a war (or a moonshot), what is required probably looks more like a counterinsurgency operation. The people are tired of being victimized, unable to have a say in their own fates. Almost any one of them would tell you: If you are going to die, it’s better to die with a purpose.

The patients enlisted so far, however, have joined almost by accident. Sharon, who continues to live in Florida without any sign of cancer, explained how thoroughly her good fortune has depended on her circumstances. Her son-in-law, an oncologist, pointed her to Sloan Kettering, and she could afford to fly up every four weeks to participate in the trial. “I think about the people who would have trouble with funds, and it breaks my heart,” she said. If Grace had not happened to live near Boston, the odds that she could have laid eyes on any of her grandchildren — or contributed to science — are long indeed. Carole Arenson, who has continued to do well on everolimus, found a place in the basket trial only because she had Foundation Medicine, a company in Cambridge, Mass., sequence her tumor, revealing the crucial mutation. “I’m as happy to see you,” Carole recalled telling a doctor involved with the trial, “as you are to see me.”

This haphazard approach has led to a chicken-­and-­egg problem that is among the most obvious obstacles to progress in precision oncology. In order to run basket trials, researchers must find patients with the right mutations. But this has proved difficult, because most patients aren’t having sequences done: Insurance generally doesn’t cover it. The reason? Because, insurance companies point out, there is not yet enough evidence that it will be clinically useful. The way to gather this evidence? Basket trials.

José Baselga, the physician in chief and chief medical officer at Sloan Kettering, told me that his hospital has a number of quite promising basket trials running but is struggling to find enough patients. One analysis published last year found that patients in genetically targeted trials are seeing better outcomes than those in traditional trials. Yet if patients who would qualify aren’t fortunate enough to be at cancer centers like Sloan Kettering or Dana-­Farber that run sequencing programs supported by philanthropic money, they either need to pay for it themselves or they are out of luck — and so is cancer research. Baselga, in conversations with Biden, has argued for a change in policy: If Medicare covered sequencing, private insurance would follow, opening up precision medicine to many more people.

It’s a problem of scale. Sloan Kettering, Dana-­Farber and several other top cancer hospitals are pooling their findings so that oncologists can search through cases, about 20,000 so far, to see what mutations were found, what drugs were tried and how patients responded. The National Cancer Institute’s Exceptional Responders Initiative has accumulated about 50 confirmed cases from around the country. Fifty exceptional responders is a large number, but it is also small. The same could be said of 20,000 cancer cases, annotated with genetic and clinical information: large, unprecedented and also not nearly enough.

For thousands of years, deep thinkers about military strategy have understood that wars are not won in the way the public imagines. Gen. Robert H. Barrow, who served four years as commandant of the United States Marine Corps, is credited with saying that “amateurs talk about tactics, but professionals study logistics.” Science has revealed the nature of cancer, and also created new means to gather intelligence on the foe. Solitary engagements can reveal new weaknesses to exploit. Does anyone truly imagine prevailing without bringing the fight everywhere — without matching cancer in its inventiveness, its nimbleness, its sheer relentlessness?

On a bitter morning in January, I visited Grace at home. When I stepped into the entryway, she stood at the top of some steps, wearing a purple top, black leggings and a pair of comfy black slippers. From a television, I made out a voice that could be only Elmo. Grace smiled.

She took a seat on a sofa with Jaelynn, her 2-year-old granddaughter, who sat in an off-­white cable-­knit sweater watching the TV and occasionally pushing her fine black hair from her face. On the wall hung a photograph of Faial, the Portuguese island where Grace’s father, who went by Mestre Simao, had been a ferry captain. Simao was beloved for braving severe storms to fetch people in distress from a nearby island and deliver them to the Faial hospital. He would tie himself to the wheel. Sometimes he returned with a cockpit window blown out.

Grace showed me a video on her phone from 2013, when a new ferry arrived at the island: The Mestre Simao, named for her father. With its lime green and dark blue bow, the boat made its way in from the ocean, trailed by a tug. Jaelynn stood next to Grace, enraptured as the scene unfolded, a hand resting on her grandmother’s leg.

Sitting there, I found myself wondering if something happened during one of Simao’s storm runs. I imagined a gravely ill man, tied down for safety, the sea enraged. The man would have been praying, and he would have known that his only earthly hope was Simao, up in the cockpit, refusing to panic as the marine glass shattered in his face. Was there a moment when this was somehow noted — when some beneficence was granted to Simao’s youngest, little Grace, who always took his lunch to the docks?

The trailing tug began pumping ocean water, two celebratory arches in the air. “Water!” Jaelynn shouted. “I know, I know,” Grace said. “Look, it’s so pretty.” The boats circled. “You want to go someday on a ship?” Grace asked. Jaelynn’s eyes kept to the screen. It was morning in the Azores, and the light hit low. “Yeah,” she said.

A few months later, Grace began coughing up blood. Joe rushed her to the emergency room: A tumor in her lung was growing again. The Takeda Oncology drug had been good for six months. Grace went through a round of radiation on the lung and then started nivolumab, a therapy that helps the immune system attack tumors. Earlier this month, though, she went to the hospital with dizziness and a severe headache. Scans showed metastasis to the brain.

Lying flat in a bed on the 12th floor of Brigham and Women’s Hospital, Grace assured Lorch that her minister was praying for him too, as he pondered his options: for her but also for what science might still learn from her remarkable case. The nivolumab was out, but Lorch did notice that the drug seemed to have been working around her lung — several tumors shrank — which is significant because doctors don’t know who will respond to the drug. He and his colleagues plan to take what they’ve learned about the genetics of Grace’s cancer and compare it with evidence, from her blood, of the drug’s activity. This might help the next patient. Grace may have yet more to give.

The story of modern cancer research begins, somewhat improbably, with the sea urchin. In the first decade of the 20th century, the German biologist Theodor Boveri discovered that if he fertilized sea-urchin eggs with two sperm rather than one, some of the cells would end up with the wrong number of chromosomes and fail to develop properly. It was the era before modern genetics, but Boveri was aware that cancer cells, like the deformed sea urchin cells, had abnormal chromosomes; whatever caused cancer, he surmised, had something to do with chromosomes.

Today Boveri is celebrated for discovering the origins of cancer, but another German scientist, Otto Warburg, was studying sea-urchin eggs around the same time as Boveri. His research, too, was hailed as a major breakthrough in our understanding of cancer. But in the following decades, Warburg’s discovery would largely disappear from the cancer narrative, his contributions considered so negligible that they were left out of textbooks altogether.

Unlike Boveri, Warburg wasn’t interested in the chromosomes of sea-urchin eggs. Rather, Warburg was focused on energy, specifically on how the eggs fueled their growth. By the time Warburg turned his attention from sea-urchin cells to the cells of a rat tumor, in 1923, he knew that sea-urchin eggs increased their oxygen consumption significantly as they grew, so he expected to see a similar need for extra oxygen in the rat tumor. Instead, the cancer cells fueled their growth by swallowing up enormous amounts of glucose (blood sugar) and breaking it down without oxygen. The result made no sense. Oxygen-fueled reactions are a much more efficient way of turning food into energy, and there was plenty of oxygen available for the cancer cells to use. But when Warburg tested additional tumors, including ones from humans, he saw the same effect every time. The cancer cells were ravenous for glucose.

Warburg’s discovery, later named the Warburg effect, is estimated to occur in up to 80 percent of cancers. It is so fundamental to most cancers that a positron emission tomography (PET) scan, which has emerged as an important tool in the staging and diagnosis of cancer, works simply by revealing the places in the body where cells are consuming extra glucose. In many cases, the more glucose a tumor consumes, the worse a patient’s prognosis.

In the years following his breakthrough, Warburg became convinced that the Warburg effect occurs because cells are unable to use oxygen properly and that this damaged respiration is, in effect, the starting point of cancer. Well into the 1950s, this theory — which Warburg believed in until his death in 1970 but never proved — remained an important subject of debate within the field. And then, more quickly than anyone could have anticipated, the debate ended. In 1953, James Watson and Francis Crick pieced together the structure of the DNA molecule and set the stage for the triumph of molecular biology’s gene-centered approach to cancer. In the following decades, scientists came to regard cancer as a disease governed by mutated genes, which drive cells into a state of relentless division and proliferation. The metabolic catalysts that Warburg spent his career analyzing began to be referred to as “housekeeping enzymes” — necessary to keep a cell going but largely irrelevant to the deeper story of cancer.

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“It was a stampede,” says Thomas Seyfried, a biologist at Boston College, of the move to molecular biology. “Warburg was dropped like a hot potato.” There was every reason to think that Warburg would remain at best a footnote in the history of cancer research. (As Dominic D’Agostino, an associate professor at the University of South Florida Morsani College of Medicine, told me, “The book that my students have to use for their cancer biology course has no mention of cancer metabolism.”) But over the past decade, and the past five years in particular, something unexpected happened: Those housekeeping enzymes have again become one of the most promising areas of cancer research. Scientists now wonder if metabolism could prove to be the long-sought “Achilles’ heel” of cancer, a common weak point in a disease that manifests itself in so many different forms.

There are typically many mutations in a single cancer. But there are a limited number of ways that the body can produce energy and support rapid growth. Cancer cells rely on these fuels in a way that healthy cells don’t. The hope of scientists at the forefront of the Warburg revival is that they will be able to slow — or even stop — tumors by disrupting one or more of the many chemical reactions a cell uses to proliferate, and, in the process, starve cancer cells of the nutrients they desperately need to grow.

Even James Watson, one of the fathers of molecular biology, is convinced that targeting metabolism is a more promising avenue in current cancer research than gene-centered approaches. At his office at the Cold Spring Harbor Laboratory in Long Island, Watson, 88, sat beneath one of the original sketches of the DNA molecule and told me that locating the genes that cause cancer has been “remarkably unhelpful” — the belief that sequencing your DNA is going to extend your life “a cruel illusion.” If he were going into cancer research today, Watson said, he would study biochemistry rather than molecular biology.

“I never thought, until about two months ago, I’d ever have to learn the Krebs cycle,” he said, referring to the reactions, familiar to most high-school biology students, by which a cell powers itself. “Now I realize I have to.”

Born in 1883 into the illustrious Warburg family, Otto Warburg was raised to be a science prodigy. His father, Emil, was one of Germany’s leading physicists, and many of the world’s greatest physicists and chemists, including Albert Einstein and Max Planck, were friends of the family. (When Warburg enlisted in the military during World War I, Einstein sent him a letter urging him to come home for the sake of science.) Those men had explained the mysteries of the universe with a handful of fundamental laws, and the young Warburg came to believe he could bring that same elegant simplicity and clarity to the workings of life. Long before his death, Warburg was considered perhaps the greatest biochemist of the 20th century, a man whose research was vital to our understanding not only of cancer but also of respiration and photosynthesis. In 1931 he won the Nobel Prize for his work on respiration, and he was considered for the award on two other occasions — each time for a different discovery. Records indicate that he would have won in 1944, had the Nazis not forbidden the acceptance of the Nobel by German citizens.

That Warburg was able to live in Germany and continue his research throughout World War II, despite having Jewish ancestry and most likely being gay, speaks to the German obsession with cancer in the first half of the 20th century. At the time, cancer was more prevalent in Germany than in almost any other nation. According to the Stanford historian Robert Proctor, by the 1920s Germany’s escalating cancer rates had become a “major scandal.” A number of top Nazis, including Hitler, are believed to have harbored a particular dread of the disease; Hitler and Joseph Goebbels took the time to discuss new advances in cancer research in the hours leading up to the Nazi invasion of the Soviet Union. Whether Hitler was personally aware of Warburg’s research is unknown, but one of Warburg’s former colleagues wrote that several sources told him that “Hitler’s entourage” became convinced that “Warburg was the only scientist who offered a serious hope of producing a cure for cancer one day.”

Although many Jewish scientists fled Germany during the 1930s, Warburg chose to remain. According to his biographer, the Nobel Prize-winning biochemist Hans Krebs, who worked in Warburg’s lab, “science was the dominant emotion” of Warburg’s adult life, “virtually subjugating all other emotions.” In Krebs’s telling, Warburg spent years building a small team of specially trained technicians who knew how to run his experiments, and he feared that his mission to defeat cancer would be set back significantly if he had to start over. But after the war, Warburg fired all the technicians, suspecting that they had reported his criticisms of the Third Reich to the Gestapo. Warburg’s reckless decision to stay in Nazi Germany most likely came down to his astonishing ego. (Upon learning he had won the Nobel Prize, Warburg’s response was, “It’s high time.”)

“Modesty was not a virtue of Otto Warburg,” says George Klein, a 90-year-old cancer researcher at the Karolinska Institute in Sweden. As a young man, Klein was asked to send cancer cells to Warburg’s lab. A number of years later, Klein’s boss approached Warburg for a recommendation on Klein’s behalf. “George Klein has made a very important contribution to cancer research,” Warburg wrote. “He has sent me the cells with which I have solved the cancer problem.” Klein also recalls the lecture Warburg gave in Stockholm in 1950 at the 50th anniversary of the Nobel Prize. Warburg drew four diagrams on a blackboard explaining the Warburg effect, and then told the members of the audience that they represented all that they needed to know about the biochemistry of cancer.

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Warburg was so monumentally stubborn that he refused to use the word “mitochondria,” even after it had been widely accepted as the name for the tiny structures that power cells. Instead Warburg persisted in calling them “grana,” the term he came up with when he identified those structures as the site of cellular respiration. Few things would have been more upsetting to him than the thought of Nazi thugs chasing him out of the beautiful Berlin institute, modeled after a country manor and built specifically for him. After the war, the Russians approached Warburg and offered to erect a new institute in Moscow. Klein recalls that Warburg told them with great pride that both Hitler and Stalin had failed to move him. As Warburg explained to his sister: “Ich war vor Hitler da” — “I was here before Hitler.”

Imagine two engines, the one being driven by complete and the other by incomplete combustion of coal,” Warburg wrote in 1956, responding to a criticism of his hypothesis that cancer is a problem of energy. “A man who knows nothing at all about engines, their structure and their purpose may discover the difference. He may, for example, smell it.”

The “complete combustion,” in Warburg’s analogy, is respiration. The “incomplete combustion,” turning nutrients into energy without oxygen, is known as fermentation. Fermentation provides a useful backup when oxygen can’t reach cells quickly enough to keep up with demand. (Our muscle cells turn to fermentation during intense exercise.) Warburg thought that defects prevent cancer cells from being able to use respiration, but scientists now widely agree that this is wrong. A growing tumor can be thought of as a construction site, and as today’s researchers explain it, the Warburg effect opens the gates for more and more trucks to deliver building materials (in the form of glucose molecules) to make “daughter” cells.

If this theory can explain the “why” of the Warburg effect, it still leaves the more pressing question of what, exactly, sets a cell on the path to the Warburg effect and cancer. Scientists at several of the nation’s top cancer hospitals have spearheaded the Warburg revival, in hopes of finding the answer. These researchers, typically molecular biologists by training, have turned to metabolism and the Warburg effect because their own research led each of them to the same conclusion: A number of the cancer-causing genes that have long been known for their role in cell division also regulate cells’ consumption of nutrients.

Craig Thompson, the president and chief executive of the Memorial Sloan Kettering Cancer Center, has been among the most outspoken proponents of this renewed focus on metabolism. In Thompson’s analogy, the Warburg effect can be thought of as a social failure: a breakdown of the nutrient-sharing agreement that single-celled organisms signed when they joined forces to become multicellular organisms. His research showed that cells need to receive instructions from other cells to eat, just as they require instructions from other cells to divide. Thompson hypothesized that if he could identify the mutations that lead a cell to eat more glucose than it should, it would go a long way toward explaining how the Warburg effect and cancer begin. But Thompson’s search for those mutations didn’t lead to an entirely new discovery. Instead, it led him to AKT, a gene already well known to molecular biologists for its role in promoting cell division. Thompson now believes AKT plays an even more fundamental role in metabolism.

The protein created by AKT is part of a chain of signaling proteins that is mutated in up to 80 percent of all cancers. Thompson says that once these proteins go into overdrive, a cell no longer worries about signals from other cells to eat; it instead stuffs itself with glucose. Thompson discovered he could induce the “full Warburg effect” simply by placing an activated AKT protein into a normal cell. When that happens, Thompson says, the cells begin to do what every single-celled organism will do in the presence of food: eat as much as it can and make as many copies of itself as possible. When Thompson presents his research to high-school students, he shows them a slide of mold spreading across a piece of bread. The slide’s heading — “Everyone’s first cancer experiment” — recalls Warburg’s observation that cancer cells will carry out fermentation at almost the same rate of wildly growing yeasts.

Just as Thompson has redefined the role of AKT, Chi Van Dang, director of the Abramson Cancer Center at the University of Pennsylvania, has helped lead the cancer world to an appreciation of how one widely studied gene can profoundly influence a tumor’s metabolism. In 1997, Dang became one of the first scientists to connect molecular biology to the science of cellular metabolism when he demonstrated that MYC — a so-called regulator gene well known for its role in cell proliferation — directly targets an enzyme that can turn on the Warburg effect. Dang recalls that other researchers were skeptical of his interest in a housekeeping enzyme, but he stuck with it because he came to appreciate something critical: Cancer cells can’t stop eating.

Unlike healthy cells, growing cancer cells are missing the internal feedback loops that are designed to conserve resources when food isn’t available. They’re “addicted to nutrients,” Dang says; when they can’t consume enough, they begin to die. The addiction to nutrients explains why changes to metabolic pathways are so common and tend to arise first as a cell progresses toward cancer: It’s not that other types of alterations can’t arise first, but rather that, when they do, the incipient tumors lack the access to the nutrients they need to grow. Dang uses the analogy of a work crew trying to put up a building. “If you don’t have enough cement, and you try to put a lot of bricks together, you’re going to collapse,” he says.

Metabolism-centered therapies have produced some tantalizing successes. Agios Pharmaceuticals, a company co-founded by Thompson, is now testing a drug that treats cases of acute myelogenous leukemia that have been resistant to other therapies by inhibiting the mutated versions of the metabolic enzyme IDH 2. In clinical trials of the Agios drug, nearly 40 percent of patients who carry these mutations are experiencing at least partial remissions.

Researchers working in a lab run by Peter Pedersen, a professor of biochemistry at Johns Hopkins, discovered that a compound known as 3-bromopyruvate can block energy production in cancer cells and, at least in rats and rabbits, wipe out advanced liver cancer. (Trials of the drug have yet to begin.) At Penn, Dang and his colleagues are now trying to block multiple metabolic pathways at the same time. In mice, this two-pronged approach has been able to shrink some tumors without debilitating side effects. Dang says the hope is not necessarily to find a cure but rather to keep cancer at bay in a “smoldering quiet state,” much as patients treat their hypertension.

Warburg, too, appreciated that a tumor’s dependence upon a steady flow of nutrients might eventually prove to be its fatal weakness. Long after his initial discovery of the Warburg effect, he continued to research the enzymes involved in fermentation and to explore the possibility of blocking the process in cancer cells. The challenge Warburg faced then is the same one that metabolism researchers face today: Cancer is an incredibly persistent foe. Blocking one metabolic pathway has been shown to slow down and even stop tumor growth in some cases, but tumors tend to find another way. “You block glucose, they use glutamine,” Dang says, in reference to another primary fuel used by cancers. “You block glucose and glutamine, they might be able to use fatty acids. We don’t know yet.”

Given Warburg’s own story of historical neglect, it’s fitting that what may turn out to be one of the most promising cancer metabolism drugs has been sitting in plain sight for decades. That drug, metformin, is already widely prescribed to decrease the glucose in the blood of diabetics (76.9 million metformin prescriptions were filled in the United States in 2014). In the years ahead, it’s likely to be used to treat — or at least to prevent — some cancers. Because metformin can influence a number of metabolic pathways, the precise mechanism by which it achieves its anticancer effects remains a source of debate. But the results of numerous epidemiological studies have been striking. Diabetics taking metformin seem to be significantly less likely to develop cancer than diabetics who don’t — and significantly less likely to die from the disease when they do.

Near the end of his life, Warburg grew obsessed with his diet. He believed that most cancer was preventable and thought that chemicals added to food and used in agriculture could cause tumors by interfering with respiration. He stopped eating bread unless it was baked in his own home. He would drink milk only if it came from a special herd of cows, and used a centrifuge at his lab to make his cream and butter.

Warburg’s personal diet is unlikely to become a path to prevention. But the Warburg revival has allowed researchers to develop a hypothesis for how the diets that are linked to our obesity and diabetes epidemics — specifically, sugar-heavy diets that can result in permanently elevated levels of the hormone insulin — may also be driving cells to the Warburg effect and cancer.

The insulin hypothesis can be traced to the research of Lewis Cantley, the director of the Meyer Cancer Center at Weill Cornell Medical College. In the 1980s, Cantley discovered how insulin, which is released by the pancreas and tells cells to take up glucose, influences what happens inside a cell. Cantley now refers to insulin and a closely related hormone, IGF-1 (insulinlike growth factor 1), as “the champion” activators of metabolic proteins linked to cancer. He’s beginning to see evidence, he says, that in some cases, “it really is insulin itself that’s getting the tumor started.” One way to think about the Warburg effect, says Cantley, is as the insulin, or IGF-1, signaling pathway “gone awry — it’s cells behaving as though insulin were telling it to take up glucose all the time and to grow.” Cantley, who avoids eating sugar as much as he can, is currently studying the effects of diet on mice that have the mutations that are commonly found in colorectal and other cancers. He says that the effects of a sugary diet on colorectal, breast and other cancer models “looks very impressive” and “rather scary.”

Elevated insulin is also strongly associated with obesity, which is expected soon to overtake smoking as the leading cause of preventable cancer. Cancers linked to obesity and diabetes have more receptors for insulin and IGF-1, and people with defective IGF-1 receptors appear to be nearly immune to cancer. Retrospective studies, which look back at patient histories, suggest that many people who develop colorectal, pancreatic or breast cancer have elevated insulin levels before diagnosis. It’s perhaps not entirely surprising, then, that when researchers want to grow breast-cancer cells in the lab, they add insulin to the tissue culture. When they remove the insulin, the cancer cells die.

“I think there’s no doubt that insulin is pro-cancer,” Watson says, with respect to the link between obesity, diabetes and cancer. “It’s as good a hypothesis as we have now.” Watson takes metformin for cancer prevention; among its many effects, metformin works to lower insulin levels. Not every cancer researcher, however, is convinced of the role of insulin and IGF-1 in cancer. Robert Weinberg, a researcher at M.I.T.’s Whitehead Institute who pioneered the discovery of cancer-causing genes in the ’80s, has remained somewhat cool to certain aspects of the cancer-metabolism revival. Weinberg says that there isn’t yet enough evidence to know whether the levels of insulin and IGF-1 present in obese people are sufficient to trigger the Warburg effect. “It’s a hypothesis,” Weinberg says. “I don’t know if it’s right or wrong.”

During Warburg’s lifetime, insulin’s effects on metabolic pathways were even less well understood. But given his ego, it’s highly unlikely that he would have considered the possibility that anything other than damaged respiration could cause cancer. He died sure that he was right about the disease. Warburg framed a quote from Max Planck and hung it above his desk: “A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die.”

The bone-marrow biopsy took about 20 minutes. It was 10 o’clock on an unusually chilly morning in New York in April, and Donna M., a self-possessed 78-year-old woman, had flown in from Chicago to see me in my office at Columbia University Medical Center. She had treated herself to orchestra seats for “The Humans” the night before, and was now waiting in the room as no one should be asked to wait: pants down, spine curled, knees lifted to her chest — a grown woman curled like a fetus. I snapped on sterile gloves while the nurse pulled out a bar cart containing a steel needle the length of an index finger. The rim of Donna’s pelvic bone was numbed with a pulse of anesthetic, and I drove the needle, as gently as I could, into the outer furl of bone. A corkscrew of pain spiraled through her body as the marrow was pulled, and then a few milliliters of red, bone-flecked sludge filled the syringe. It was slightly viscous, halfway between liquid and gel, like the crushed pulp of an overripe strawberry.

I had been treating Donna in collaboration with my colleague Azra Raza for six years. Donna has a preleukemic syndrome called myelodysplastic syndrome, or MDS, which affects the bone marrow and blood. It is a mysterious disease with few known treatments. Human bone marrow is normally a site for the genesis of most of our blood cells — a white-walled nursery for young blood. In MDS, the bone-marrow cells acquire genetic mutations, which force them to grow uncontrollably — but the cells also fail to mature into blood, instead dying in droves. It is a dual curse. In most cancers, the main problem is cells that refuse to stop growing. In Donna’s marrow, this problem is compounded by cells that refuse to grow up.

Though there are commonalities among cancers, of course, every tumor behaves and moves — “thinks,” even — differently. Trying to find a drug that fits Donna’s cancer, Raza and I have administered a gamut of medicines. Throughout all this, Donna has been a formidable patient: perennially resourceful, optimistic and willing to try anything. (Every time I encounter her in the clinic, awaiting her biopsy with her characteristic fortitude, it is the doctor, not the patient, who feels curled and small.) She has moved nomadically from one trial to another, shuttling from city to city, and from one drug to the next, through a landscape more desolate and exhilarating than most of us can imagine; Donna calls it her “serial monogamy” with different medicines. Some of these drugs have worked for weeks, some for months — but the transient responses have given way to inevitable relapses. Donna is getting exhausted.

Her biopsy that morning was thus part routine and part experiment. Minutes after the marrow was drawn into the syringe, a technician rushed the specimen to the lab. There he extracted the cells from the mixture and pipetted them into tiny grain-size wells, 500 cells to a well. To each well — about 1,000 in total — he will add a tiny dab of an individual drug: prednisone, say, to one well, procarbazine to the next and so forth. The experiment will test about 300 medicines (many not even meant for cancer) at three different doses to assess the effects of the drugs on Donna’s cells.

Bathed in a nutrient-rich broth suffused with growth factors, the cells will double and redouble in an incubator over the course of the following two weeks, forming a lush outgrowth of malignant cells — cancer abstracted in a dish. A computer, taught to count and evaluate cells, will then determine whether any of the drugs killed the cancerous cells or forced them to mature into nearly normal blood. Far from relying on data from other trials, or patients, the experiment will test Donna’s own cancer for its reactivity against a panel of medicines. Cells, not bodies, entered this preclinical trial, and the results will guide her future treatment.

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I explained all this to Donna. Still, she had a question: What would happen if the drug that appeared to be the most promising proved unsuccessful?

“Then we’ll try the next one,” I told her. “The experiment, hopefully, will yield more than one candidate, and we’ll go down the list.”

“Will the medicine be like chemotherapy?”

“It might, or it might not. The drug that we end up using might be borrowed from some other disease. It might be an anti-inflammatory pill, or an asthma drug. It might be aspirin, for all we know.”

My conversation with Donna reflected how much cancer treatment has changed in the last decade. I grew up as an oncologist in an era of standardized protocols. Cancers were lumped into categories based on their anatomical site of origin (breast cancer, lung cancer, lymphoma, leukemia), and chemotherapy treatment, often a combination of toxic drugs, was dictated by those anatomical classifications. The combinations — Adriamycin, bleomycin, vinblastine and dacarbazine, for instance, to treat Hodgkin’s disease — were rarely changed for individual patients. The prospect of personalizing therapy was frowned upon: The more you departed from the standard, the theory ran, the more likely the patient would end up being undertreated or improperly managed, risking recurrence. In hospitals and clinics, computerized systems were set up to monitor an oncologist’s compliance with standard therapy. If you chose to make an exception for a particular patient, you had to justify the choice with an adequate excuse. Big Chemo was watching you.

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I memorized the abbreviated names of combination chemo — the first letter of each drug — for my board exams, and I spouted them back to my patients during my clinic hours. There was something magical and shamanic about the multiletter contractions. They were mantras imbued with promise and peril: A.B.V.D. for Hodgkin’s, C.M.F. for breast cancer, B.E.P. for testicular cancer. The lingo of chemotherapists was like a secret code or handshake; even the capacity to call such baleful poisons by name made me feel powerful. When my patients asked me for statistical data, I had numbers at my fingertips. I could summon the precise chance of survival, the probability of relapse, the chance that the chemo would make them infertile or cause them to lose their hair. I felt omniscient.

Yet as I spoke to Donna that morning, I realized how much that omniscience has begun to wane — unleashing a more experimental or even artisanal approach in oncology. Most cancer patients are still treated with those hoary standardized protocols, still governed by the anatomical lumping of cancer. But for patients like Donna, for whom the usual treatments fail to work, oncologists must use their knowledge, wit and imagination to devise individualized therapies. Increasingly, we are approaching each patient as a unique problem to solve. Toxic, indiscriminate, cell-killing drugs have given way to nimbler, finer-fingered molecules that can activate or deactivate complex pathways in cells, cut off growth factors, accelerate or decelerate the immune response or choke the supply of nutrients and oxygen. More and more, we must come up with ways to use drugs as precision tools to jam cogs and turn off selective switches in particular cancer cells. Trained to follow rules, oncologists are now being asked to reinvent them.

The thought that every individual cancer might require a specific individualized treatment can be profoundly unsettling. Michael Lerner, a writer who worked with cancer patients, once likened the experience of being diagnosed with cancer to being parachuted out of a plane without a map or compass; now it is the oncologist who feels parachuted onto a strange landscape, with no idea which way to go. There are often no previous probabilities, and even fewer certainties. The stakes feel higher, the successes more surprising and the failures more personal. Earlier, I could draw curtain upon curtain of blame around a patient. When she did not respond to chemotherapy, it was her fault: She failed. Now if I cannot find a tool in the growing kit of drugs to target a cancer’s vulnerabilities, the vector feels reversed: It is the doctor who has failed.

Yet the mapless moment that we are now in may also hold more promise for patients than any that has come before — even if we find the known world shifting under our feet. We no longer have to treat cancer only with the blunt response of standard protocols, in which the disease is imagined as a uniform, if faceless, opponent. Instead we are trying to assess the particular personality and temperament of an individual illness, so that we can tailor a response with extreme precision. It’s the idiosyncratic mind of each cancer that we are so desperately trying to capture.

Cancer — and its treatment — once seemed simpler. In December 1969, a group of cancer advocates led by the philanthropist Mary Lasker splashed their demand for a national war on cancer in a full-page ad in The New York Times: “Mr. Nixon: You Can Cure Cancer.” This epitomized the fantasy of a single solution to a single monumental illness. For a while, the centerpiece of that solution was thought to be surgery, radiation and chemotherapy, a strategy colloquially known as “slash and burn.” Using combination chemotherapy, men and women were dragged to the very brink of physiological tolerability but then pulled back just in time to send the cancer, but not its host, careering off the edge.

Throughout the 1980s and 1990s, tens of thousands of people took part in clinical trials, which compared subjects on standard chemo combinations with others administered slightly different combinations of those drugs. Some responded well, but for many others, relapses and recurrences were routine — and gains were small and incremental for most cancers. Few efforts were made to distinguish the patients; instead, when the promised cures for most advanced malignancies failed to appear, the doses were intensified and doubled. In the Margaret Edson play “Wit,” an English professor who had ovarian cancer recalled the bewildering language of those trials by making up nonsensical names for chemotherapy drugs that had been pumped into her body: “I have survived eight treatments of hexamethophosphacil and vinplatin at the full dose, ladies and gentlemen. I have broken the record.”

To be fair, important lessons were garnered from the trials. Using combinations of chemotherapy, we learned to treat particular cancers: aggressive lymphomas and some variants of breast, testicular and colon cancers. But for most men and women with cancer, the clinical achievements were abysmal disappointments. Records were not broken — but patients were.

A breakthrough came in the 2000s, soon after the Human Genome Project, when scientists learned to sequence the genomes of cancer cells. Cancer is, of course, a genetic disease at its core. In cancer cells, mutated genes corrupt the normal physiology of growth and ultimately set loose malignant proliferation. This characteristic sits at the heart of all forms of cancer: Unlike normal cells, cancer cells have forgotten how to stop dividing (or occasionally, have forgotten how to die). But once we could sequence tens of thousands of genes in individual cancer specimens, it became clear that uniqueness dominates. Say two identical-looking breast cancers arise at the same moment in identical twins; are the mutations themselves in the two cancers identical? It’s unlikely: By sequencing the mutations in one twin’s breast cancer, we might find, say, 74 mutated genes (of the roughly 22,000 total genes in humans). In her sister’s, we might find 42 mutations, and if we looked at a third, unrelated woman with breast cancer, we might find 18. Among the three cases, there might be a mere five genes that overlap. The rest are mutations particular to each woman’s cancer.

No other human disease is known to possess this degree of genetic heterogeneity. Adult-onset diabetes, for example, is a complex genetic disease, but it appears to be dominated by variations in only about a dozen genes. Cancer, by contrast, has potentially unlimited variations. Like faces, like fingerprints — like selves — every cancer is characterized by its distinctive marks: a set of individual scars stamped on an individual genome. The iconic illness of the 20th century seems to reflect our culture’s obsession with individuality.

If each individual cancer has an individual combination of gene mutations, perhaps this variability explains the extraordinary divergences in responses to treatment. Gene sequencing allows us to identify the genetic changes that are particular to a given cancer. We can use that information to guide cancer treatment — in effect, matching the treatment to an individual patient’s cancer.

Many of the remarkable successes of cancer treatments of the last decades are instances of drugs that were matched to the singular vulnerabilities of individual cancers. The drug Gleevec, for instance, can kill leukemia cells — but only if the patient’s cancer cells happen to carry a gene mutation called BCR-ABL. Tarceva, a targeted therapy for lung cancer, works powerfully if the patient’s cancer cells happen to possess a particular mutant form of a gene; for lung-cancer patients lacking that mutation, it may be no different from taking a placebo. Because the medicines target mutations or behaviors that are specific to cancer cells (but not normal cells), many of these drugs have surprisingly minimal toxicities — a far cry from combination chemotherapies of the past.

A few days after Donna’s visit to the clinic, I went to my weekly meeting with Raza on the ninth floor of the hospital. The patient that morning was K.C., a 79-year-old woman with blood cancer. Raza has been following her disease — and keeping her alive — for a decade.

“Her tumor is evolving into acute leukemia,” Raza said. This, too, is a distinctive behavior of some cancers that we can now witness using biopsies, CT scans and powerful new techniques like gene sequencing: We can see the cancers morphing from smoldering variants into more aggressive types before our eyes.

“Was the tumor sequenced?” I asked.

“Yes, there’s a sequence,” Raza said, as we leaned toward a screen to examine it. “P53, DNMT3a and Tet2,” she read from the list of mutant genes. “And a deletion in Chromosome 5.” In K.C.’s cancer, an entire segment of the genome had been lopped off and gone missing — one of the crudest mutations that a tumor can acquire.

“How about ATRA?” I asked. We had treated a few patients carrying some of K.C.’s mutations with this drug and noted a few striking responses.

“No. I’d rather try Revlimid, but at a higher dose. She’s responded to it in the past, and the mutations remain the same. I have a hunch that it might work.”

As Raza and I returned to K.C.’s room to inform her of the plan, I couldn’t help thinking that this is what it had come down to: inklings, observations, instincts. Medicine based on premonitions. Chemo by hunch. The discussion might have sounded ad hoc to an outsider, but there was nothing cavalier about it. We parsed these possibilities with utmost seriousness. We studied sequences, considered past responses, a patient’s recent history — and then charged forward with our best guess. Our decisions were spurred by science, yes, but also a sense for the art of medicine.

Oncologists are also practicing this art in areas that rely less on genes and mutations. A week after Donna’s biopsy, I went to see Owen O’Connor, an oncologist who directs Columbia’s lymphoma center. O’Connor, in his 50s, reminds me of an amphibious all-terrain vehicle — capable of navigating across any ground. We sat in his office, with large, sunlit windows overlooking Rockefeller Plaza. For decades, he explained, oncologists had treated relapsed Hodgkin’s lymphoma in a standard manner. “There were limited options,” O’Connor said. “We gave some patients more chemotherapy, with higher doses and more toxic drugs, hoping for a response. For some, we tried to cure the disease using bone-marrow transplantation.” But the failure rate was high: About 30 percent of patients didn’t respond, and half of them died.

Then a year or two ago, he tried something new. He began to use immunological therapy to treat relapsed, refractory Hodgkin’s lymphoma. Immunological therapies come in various forms. There are antibodies: missile-like proteins, made by our own immune systems, that are designed to attack and destroy foreign microbes (antibodies can also be made artificially through genetic engineering, armed with toxins and used as “drugs” to kill cancer cells). And there are drugs that incite a patient’s own immune system to recognize and kill tumor cells, a mode of treatment that lay fallow for decades before being revived. O’Connor used both therapies and found that they worked in patients with Hodgkin’s disease. “We began to see spectacular responses,” he said.

Yet even though many men and women with relapsed Hodgkin’s lymphoma responded to immunological treatments, there were some who remained deeply resistant. “These patients were the hardest to treat,” O’Connor continued. “Their tumors seemed to be unique — a category of their own.”

Lorenzo Falchi, a fellow training with O’Connor and me, was intrigued by these resistant patients. Falchi came to our hospital from Italy, where he specialized in treating leukemias and lymphomas; his particular skill, gleaned from his experience with thousands of patients, is to look for patterns behind seemingly random bits of data. Rooting about in Columbia’s medical databases, Falchi made an astonishing discovery: The men and women who responded most powerfully to the immune-boosting therapies had invariably been pretreated with another drug called azacitidine, rarely used in lymphoma patients. A 35-year-old woman from New York with relapsed lymphoma saw her bulky nodes melt away. She had received azacitidine as part of another trial before moving on to the immunotherapy. A man, with a similar stage of cancer, had not been pretreated. He had only a partial response, and his disease grew back shortly thereafter.

Falchi and O’Connor will use this small “training set” to begin a miniature trial of patients with relapsed Hodgkin’s disease. “We will try it on just two or three patients,” Falchi told me. “We’ll first use azacitidine — intentionally, this time — and then chase it with the immune activators. I suspect that we’ll reproduce the responses that we’ve seen in our retrospective studies.” In lung cancer too, doctors have noted that pretreating patients with azacitidine can make them more responsive to immunological therapy. Falchi and O’Connor are trying to figure out why patients respond if they are pretreated with a drug that seems, at face value, to have nothing to do with the immune system. Perhaps azacitidine makes the cancer cells more recognizably foreign, or perhaps it forces immune cells to become more aggressive hunters.

Falchi and O’Connor are mixing and matching unexpected combinations of medicines based on previous responses — departing from the known world of chemotherapy. Even with the new combination, Falchi suspects, there will be resistant patients, and so he will divide these into subsets, and root through their previous responses, to determine what might make these patients resistant — grinding the data into finer and finer grains until he’s down to individualized therapy for every variant of lymphoma.

Suppose every cancer is, indeed, unique, with its own permutation of genes and vulnerabilities — a sole, idiosyncratic “mind.” It’s obviously absurd to imagine that we’ll find an individual medicine to treat each one: There are 14 million new cases of cancer in the world every year, and several million of those patients will present with advanced disease, requiring more than local or surgical treatment. Trying to individualize treatment for those cases would shatter every ceiling of cost.

But while the medical costs of personalized therapy are being debated in national forums in Washington, the patients in my modest waiting room in New York are focused on its personal costs. Insurance will not pay for “off-label” uses of medicines: It isn’t easy to convince an insurance company that you intend to use Lipitor to treat a woman with pre-leukemia — not because she has high cholesterol but because the cancer cells depend on cholesterol metabolism for their growth (in one study of a leukemia subtype, the increasing cells were highly dependent on cholesterol, suggesting that high doses of Lipitor-like drugs might be an effective treatment).

In exceptional cases, doctors can requisition pharmaceutical companies to provide the medicines free — for “compassionate use,” to use the language of the pharma world — but this process is unpredictable and time-consuming. I used to fill out such requests once every few months. Now it seems I ask for such exceptions on a weekly basis. Some are approved. A majority, unfortunately, are denied.

So doctors like Falchi and O’Connor do what they can — using their wiles not just against cancer but against a system that can resist innovation. They create minuscule, original clinical trials involving just 10 or 20 patients, a far cry from the hundred-thousand-patient trials of the ’80s and ’90s. They study these patients with monastic concentration, drawing out a cosmos of precious data from just that small group. Occasionally, a patient may choose to pay for the drugs out of his or her own pockets — but it’s a rare patient who can afford the tens of thousands of dollars that the drugs cost.

But could there be some minimal number of treatments that could be deployed to treat a majority of these cancers effectively and less expensively? More than any other scientist, perhaps, Bert Vogelstein, a cancer geneticist at Johns Hopkins University, has tackled that conundrum. The combination of genetic mutations in any individual cancer is singular, Vogelstein acknowledges. But these genetic mutations can still act through common pathways. Targeting pathways, rather than individual genes, might reorganize the way we perceive and treat cancer.

Imagine, again, the cell as a complex machine, with thousands of wheels, levers and pulleys organized into systems. The machine malfunctions in the cancer: Some set of levers and pulleys gets jammed or broken, resulting in a cell that continues to divide without control. If we focus on the individual parts that are jammed and snapped, the permutations are seemingly infinite: Every instance of a broken machine seems to have a distinct fingerprint of broken cogs. But if we focus, instead, on systems that malfunction, then the seeming diversity begins to collapse into patterns of unity. Ten components function, say, in an interconnected loop to keep the machine from tipping over on its side. Snap any part of this loop, and the end result is the same: a tipped-over machine. Another 20 components control the machine’s internal thermostat. Break any of these 20 components, and the system overheats. The number of components — 10 and 20 — are deceptive in their complexity, and can have endless permutations. But viewed from afar, only two systems in this machine are affected: stability and temperature.

Cancer, Vogelstein argues, is analogous. Most of the genes that are mutated in cancer also function in loops and circuits — pathways. Superficially, the permutations of genetic flaws might be boundless, but lumped into pathways, the complexity can be organized along the archetypal, core flaws. Perhaps these cancer pathways are like Hollywood movies; at first glance, there seems to be an infinite array of plot lines in an infinite array of settings — gold-rush California, the Upper West Side, a galaxy far, far away. But closer examination yields only a handful of archetypal narratives: boy meets girl, stranger comes to town, son searches for father.

How many such pathways, or systems, operate across a subtype of cancer? Looking at one cancer, pancreatic, and mapping the variations in mutated genes across hundreds of specimens, Vogelstein’s team proposed a staggeringly simple answer: 12. (One such “core pathway,” for instance, involves genes that enable cells to invade other tissues. These genes normally allow cells to migrate through parts of the body — but in cancer, migration becomes distorted into invasion.) If we could find medicines that could target these 12 core pathways, we might be able to attack most pancreatic cancers, despite their genetic diversity. But that means inventing 12 potential ways to block these core paths — an immense creative challenge for scientists, considering that they haven’t yet figured out how to target more than, at best, one or two.

Immunological therapies provide a second solution to the impasse of unlimited diversity. One advantage of deploying a patient’s own immune system against cancer is that immunological cells are generally agnostic to the mutations that cause a particular cancer’s growth. The immune system was designed to spot differences in the superficial features of a diseased or foreign cell, thereby identifying and killing it. It cares as little about genes as an intercontinental ballistic missile cares about the email addresses, or dietary preferences, of the population that it has been sent to destroy.

A few years ago, in writing a history of cancer, I interviewed Emil Freireich. Freireich, working with Emil Frei at the National Cancer Institute in the 1960s and ’70s, stumbled on the idea of deploying multiple toxic drugs simultaneously to treat cancer — combination chemotherapy. They devised one of the first standard protocols — vincristine, Adriamycin, methotrexate and prednisone, known as VAMP — to treat pediatric leukemias. Virtually nothing about the VAMP protocol was individualized (although doses could be reduced if needed). In fact, doctors were discouraged from trying alternatives to the formula.

Yet as Freireich recalled, long before they came up with the idea for a protocol, there were small, brave experiments; before trials, there was trial and error. VAMP was brought into existence through grit, instinct and inspired lunges into the unknown. Vincent T. DeVita Jr., who worked with Freireich in the 1960s, wrote a book, “The Death of Cancer,” with his daughter, Elizabeth DeVita-Raeburn. In it, he recalled a time when the leukemic children in Freireich’s trial were dying of bacterial meningitis during treatment. The deaths threatened the entire trial: If Freireich couldn’t keep the children alive during the therapy, there would be no possibility of remission. They had an antibiotic that could kill the microbe, but the medicine wouldn’t penetrate the blood-brain barrier. So Freireich decided to try something that pushed the bounds of standard practice. He ordered DeVita, his junior, to inject it directly into the spinal cords of his patients. It was an extreme example of off-label use of the drug: The medicine was not meant for use in the cord. DeVita writes:

“The first time Freireich told me to do it, I held up the vial and showed him the label, thinking that he’d possibly missed something. ‘It says right on there, “Do not use intrathecally,” ’ I said. Freireich glowered at me and pointed a long, bony finger in my face. ‘Do it!’ he barked. I did it, though I was terrified. But it worked every time.”

When I asked Freireich about that episode and about what he would change in the current landscape of cancer therapy, he pointed to its extreme cautiousness. “We would never have achieved anything in this atmosphere,” he said. The pioneer of protocols pined for a time before there were any protocols.

Medicine needs standards, of course, otherwise it can ramble into dangerous realms, compromising safety and reliability. But cancer medicine also needs a healthy dose of Freireich: the desire to read between the (guide)lines, to reimagine the outer boundaries, to perform the experiments that become the standards of the future. In January, President Obama introduced an enormous campaign for precision medicine. Cancer is its molten centerpiece: Using huge troves of data, including gene sequences of hundreds of thousands of specimens and experiments performed in laboratories nationwide, the project’s goal is to find individualized medicines for every patient’s cancer. But as we wait for that decades-long project to be completed, oncologists still have to treat patients now. To understand the minds of individual cancers, we are learning to mix and match these two kinds of learning — the standard and the idiosyncratic — in unusual and creative ways. It’s the kind of medicine that so many of us went to medical school to learn, the kind that we’d almost forgotten how to practice.

This Year, the American Academy of Pediatrics asserted that the advantages of circumcising boys outweighed the potential risks from the procedure. They reported health advantages that, whilst not great enough to warrant a suggestion for those males to endure the process, were significant enough that it ought to be open to all, which ought to be covered with insurance. Not lengthy after, the CDC agreed.

Let’s consider the evidence. For a long time, pediatricians have reported studies that demonstrate that being uncircumcised is really a risk factor for creating a urinary system infection. They indicate research that implies that circumcised penises have ‘abnormal’ amounts of bacteria and yeast. Much more compelling, cohort studies demonstrated there would be a tenfold rise in the speed of urinary system infection in boys who have been uncircumcised versus individuals who have been.

The particular rates of urinary system infection were 1.1 % versus .1 %, to have an absolute rate difference of just one percent. Which means that 100 boys will have to be circumcised to avoid one urinary system infection. Other v-day the amount may be greater.

It’s very hard to reason that this decrease may be worth a lasting, surgical treatment. It’s especially difficult to argue considering that we don’t genuinely have data from randomized controlled trials. It’s entirely possible that there’s another thing different between boys who have been circumcised and individuals who weren’t, especially since the great majority (greater than 80 %) of boys during these studies were circumcised. Regardless, this quantity of benefit appears to pass through the brink for coverage by insurance (that is low), so the process is available.

Another advantage sometimes pointed out is really a reduced chance of male organ cancer. Situation control research has reported that uncircumcised guys have a 3 occasions greater possibility of developing male organ cancer. Again, this really is relative: Male organ cancer is extremely rare within the U . s . States, therefore the actual risk reduction from circumcision is extremely, really small. It’s believed which more than 300,000 infants should be circumcised to avoid one situation of male organ cancer.

Some reason that circumcision can help to eliminate the risk of contracting a sexually transmitted infection later in existence. An organized overview of 26 studies discovered that circumcised males are in a lower chance of syphilis or chancroid. There can be some protection against herpes, but it’s decreased.

The most powerful situation for circumcision can be created like a benefit from the transmission of H.I.V. In Africa, where H.I.V. is a lot more prevalent, randomized controlled trials of circumcision happen to be performed. The outcomes were quite convincing. Absolute rate reductions of just one-2 percent over one or two years were seen. Some estimate that for 10-20 males circumcised, one less man might contract H.I.V. more than a lifetime. One study likened circumcision to some vaccine of high effectiveness.

Again, though, these results affect countries having a much greater prevalence of H.I.V. than we have seen within the U . s . States. The security afforded, therefore, far less significant here.

Opponents of circumcision indicate its potential downsides. Surgical complications, while rare, are more than zero. Discomfort is an issue too evidence exists both to aid and rebut the concept infants recover rapidly.

More prominent concerns concentrate on sexual function and gratification. Opponents reason that the foreskin, like much of your penis, contains many nerve endings. Additionally, it protects the mind of your penis without them, your penis might dwindle sensitive with time.

But performs this really happen? Research conducted recently within the Journal of Urology, discussed within the New You are able to Occasions, measured male organ sensitivity in circumcised and uncircumcised men and located no real difference. It was not the very first, or even the best, study to check out this.

A randomized controlled trial in excess of 2,700 men in Kenya discovered that after circumcision they experienced elevated sensitivity, and they had an simpler time reaching orgasm. An organized review and meta-analysis discovered that circumcision was unrelated to early ejaculation, erection dysfunction or difficulty achieving orgasm.

Total, evidence quarrelling for and against circumcision fails to create a compelling situation either in direction. The advantages, while perhaps real, are small likewise the harms. In such instances, we usually leave the choice to the individual.

There’s, obviously, a moral problem here, because the option is more often than not produced by parents, not through the boys themselves. Circumcision is irreversible, and lots of argue, quite stridently, this is “genital mutilation” inflicted on children never ever.

All cards up for grabs: I’m Jewish, and I’m circumcised, much like both my sons. The process includes a spiritual weight within my community. When faced by individuals using terms like mutilation, I generally recoil. Circumcising my boys would be a personal decision in my wife and me, and that i comprehend the various arguments for and against. People angry relating to this choice appear to assume that people haven’t completely considered it.

I additionally accept the understanding that it is entirely possible that the kids may have selected differently. But we have to acknowledge that oldsters make many, many decisions for his or her kids with a larger and much more significant effect on them than circumcision. That’s what parents do. Presuming that this is actually the most consequential one we may make about our boys’ lives, and focusing a lot attention onto it — when evidence makes the need for either choice unclear — appears from proportion.

That does not mean opponents do not have a place. Circumcision is a lot rarer in many other industrialized countries. Health organizations in individuals countries don’t advocate the process once we do within the U . s . States. A disagreement may also be designed for waiting until boys are of sufficient age to consider on their own. Numerous factors make that difficult, though. It’s a far more complicated procedure then, with greater risks and greater costs.

Considering that religion and culture are tangled up within this, it’s obvious this issue will not be made the decision soon. It is also obvious that evidence perform anyone’s choice simpler. Within the finish, the choice whether parents opt to obtain their babies circumcised will stay an individual one.

Not lengthy ago, several aging elite distance runners met up, so that as they reminisced about old occasions, a well-recognized subject came about: Regardless of how much they train, regardless of how much they push themselves, their finest occasions are in it.

Howard Nippert broached it first. He was running a few days ago, he told his buddies, and feeling as though he is at the groove, feeling great, just flying along because he did several years ago. He then made the error of searching at his watch. It had been telling him something a great deal diverse from what he was feeling.

“I know precisely your feelings,Inches stated uncle, Steve Spence, who’s 53. Both males are still great runners coupled with stellar running careers. Nippert, who’s 50 along with a running coach in Pearisburg, Veterans administration., would be a world-class ultramarathoner along with a former person in the U . s . States track and field team. Spence, who won a bronze medal within the marathon in the world titles in 1991, coaches runners at Shippensburg College in Pennsylvania but still runs miles race each year in under 5 minutes. But, he laments, “I used so that you can operate a marathon at this pace.”

No-one can indicate precisely why performance begins to decline as we grow older. One thing muscles weaken? Why are they going to when you have used them regularly inside a sport? One thing the center can’t pump just as much bloodstream? Why does which happen? Largest, it makes sense a trade-off between speed and endurance. If you wish to go fast, you cannot continue the interest rate how you accustomed to. If you wish to go far, you cannot get it done fast, states Hirofumi Tanaka, director from the Cardiovascular Aging Research Laboratory in the College of Texas at Austin.

The maturing effect is inevitable, and today runners may even track what to anticipate. It’s as though at one time clock for aging, and in contrast to nonrunners — who’ve only such things as wrinkles and grey hair to put into practice — runners come with an exact schedule which will predict how their performance will decline.

That schedule is online of Ray Fair, a professor within the financial aspects department at Yale, who had been inspired to obtain the patterns of slowdowns when their own running performance started to say no. It makes sense a table. Place inside your ideal time ever to have an event, say a ten-kilometer race, and just how old you had been whenever you ran it. The table then shows how quickly you might have run it whenever you were more youthful and just how fast you will be able to run it now so that as you grow even older.

“Some repeat the site altered their existence,” Fair stated. “They know they’ll slow lower because they get older, but because lengthy because they slow lower around the website states they’ll, they’re fine.”

For Fair, he is not as happy.

“I am this is not on my line,” he stated. “I am worse than I ought to be however i am looking to get back.”

But being at risk means not that which you were before, and that is one hard adjustment for a lot of former elite runners.

“I still run every single day,Inches Nippert stated, “but it’s a difficult transition to simply being just a day to day runner.”

Sometimes, just like Mary Decker Slaney and Doriane Coleman, elite middle distance runners, the finish of the career starts insidiously by having an injuries that their aging physiques just cannot recover.

Slaney, who’s 57, ruptured her posterior tibial tendon in 1997. She’d surgery to get it reconstructed after which attempted to coach, telling herself she might get back enough where she’d been.

“For a lengthy time, I figured there is still a method to improve,Inches Slaney stated. “But eventually you’re able to a place where it becomes clear that occurring. I couldn’t run, I possibly could only jog and also to me which was disheartening. But after about ten years, I made the decision: O.K. I’ll jog since i can’t do other things.”

She was saved, she stated, when she discovered a kind of mixture of elliptical mix-trainer and bicycle that they may use on the highway outdoors her home in Eugene, Ore. “It may be the nearest factor to running without really running,” she stated. “I got on a single the very first time and within ten minutes I understood I needed to get one. I figured, My dear God, I haven’t felt that means by a lengthy time.”

Slaney still hopes for running, and she or he frequently dreams she’s back around the beginning line. Her dreams even include training again. “There is certainly not to duplicate the sensation of running,” she stated.

Her friend Coleman, legislation professor at Duke College, understands very well. On her, the job-ending injuries would be a ruptured Achilles’ tendon.

“For a long time I did not possess a effective technique to transition from as being a runner where every run is really a training run, every run includes a purpose and you’re constantly conscious of time passing and distance passing,” she stated. “That’s so ingrained.”

She stored attempting to train, she stated, but “it was making me insane.” Then she reasoned with herself. “I am 55 years of age, for God’s sake,” she stated she recognized. “I don’t will need to go on training runs any longer.”

But old routine is difficult to break. Sometimes, Coleman states, when she’s on the run, feeling good, “my brain adopts its old track and i believe, ‘I can do it properly.’ ”

On individuals days, she states, “I get the interest rate a bit I type of forget how old irrrve become.Inches

But she also offers a method which has altered her existence. She leaves her watch behind. Before she sets on a run, Coleman compares the clock. When she will get back, she glances in internet marketing again.

Then she informs herself, “Ballpark.”

Correction: May 4, 2016

Articles last Wednesday concerning the aftereffect of aging on elite runners misidentified the marathon where Steve Spence won a bronze medal. It had been the 1991 world titles, and not the 1992 Olympic games.

This short article initially ran in April. We’re resurfacing it considering new guidelines in the National Institute of Allergy and Infectious Illnesses that advise giving peanuts to children early and frequently as an approach to forestall an allergic reaction.

It is articles of belief among a lot of women I understand to get rid of some foods while pregnant, from concern their children turn into allergic for them: shellfish, dairy and, first and foremost, peanuts.

After their babies arrive, they still refrain from particular foods while breast-feeding, plus they certainly maintain their children from eating them.

But research within the last couple of years has consistently proven that this avoidance frequently does more damage than good. Oftentimes, we have to do the alternative.

Moms didn’t adopt this behavior from nowhere. In 2000, the American Academy of Pediatrics released guidelines on reducing a child’s risk for developing allergic reactions. They suggested that moms “eliminate peanuts and tree nuts (e.g., almonds, walnuts, etc.) and think about eliminating eggs, cow’s milk, fish, and possibly other foods using their diets while nursing.”

Further, they suggested that youngsters at high-risk for allergic reactions get no food until six several weeks old, no milk products until 12 months old, no eggs until age 2, with no peanuts, nuts or fish until age 3.

A debate continues to be raging within the healthcare system for many years about this subject. I had been a part of an organized review that examined the connection between early solid food introduction and allergic disease in youngsters. We found not good evidence to aid the concept that being uncovered to food earlier brought to persistent food allergic reactions.

To the credit, the A.A.P. altered its recommendations according to new information. In 2008, updated guidelines reported that maternal limitations during pregnancy or breast-feeding no more appeared like advice that needs to be broadly suggested. Additionally, it acknowledged there didn’t appear much need to delay the development of “allergy” foods like peanuts red carpet several weeks, round the age babies change from milk or formula to some wider selection of food.

Regrettably, this did little to alter people’s behavior. Many had already internalized the recommendation. It appeared logical for them that staying away from foods will give children a lesser opportunity to develop allergic reactions. Whether it was still being advisable to not expose children until these were six several weeks old, why don’t you carry on?

Research printed within the Colonial Journal of drugs this past year switched all this on its mind. Researchers enrolled 640 infants at high-risk for allergic reactions, between 4 and 11 several weeks old, inside a trial and randomized these to 1 of 2 groups. One of these ended up being to avoid peanut protein another ended up being to get your meals at least six grams of peanut protein per week succumbed 3 or more meals. All participants were adopted until these were five years old.

That which was most surprising within this work was that 15 % from the infants already had proof of peanut sensitivity by allergy testing. These were signed up for the trial regardless of this, and 1 / 2 of them received peanut extract each week.

The outcomes were outstanding. In the finish from the study, about 3 % of individuals uncovered to peanuts acquired a peanut allergy, compared using more than 17 % among individuals who prevented peanuts.

More surprising, should you looked just in the children who already had proof of peanut sensitivity once they were babies, less than 11 percent of individuals regularly uncovered to peanuts developed an allergic reaction. But greater than 35 % of individuals who prevented peanuts developed an allergic reaction.

Children who’d proven sensitivity to peanuts, but consumed them within their diet regularly, were less inclined to create a peanut allergy than children without sensitivity who prevented them.

Lately, follow-up outcome was printed. Following the trial ended, researchers requested all of the participants who was simply regularly consuming peanuts to prevent them for the following 12 several weeks.

In the finish of this period, once the children were 6, there wasn’t any significant rise in new peanut allergic reactions for the reason that group. Avoidance at this time made no difference. The critical requirement for exposure seems to become somewhere from infancy until age 5.

These outcome was so convincing that, once more, experts are altering their recommendations. In September 2015, the A.A.P. — together with others — contended that “health health care providers should recommend presenting peanut-that contains products in to the diets of ‘high-risk’ infants in early stages in existence.”

These changes dovetail nicely within what has been known because the hygiene hypothesis, the gist being that as we’ve made our atmosphere increasingly more sterile, our natural defenses develop differently compared to what they accustomed to. Without contact with outdoors items to fight, our defenses turn inward and toward more benign substances, resulting in elevated amounts of eczema, bronchial asthma and allergic reactions.

Obviously, lots of people accustomed to die from infections that no more threaten us due to advances, so nobody must take this like a demand residing in filth. Nor should anybody take these recent findings as advice to give babies and young children peanuts along with other foods without concern. All changes for an infant’s diet, particularly in kids with allergic reactions, ought to be done in consultation having a doctor.

Just like other areas of healthcare, however, we went too much with this reaction to peanut along with other food allergic reactions. Avoidance may also be required for individuals with severe reactions. Whenever we apply individuals same rules to everybody else, however, things can backfire.

There is lots of news now in regards to a study, printed within the medical journal BMJ, that checked out how diet affects heart health. The outcomes were unpredicted simply because they challenged the traditional thinking on fatty foods.

And also the data were early, in the late 1960s and early 1970s.

It has brought many to question why they weren’t printed formerly. It’s also put into the growing concern that with regards to diet, personal beliefs frequently trump science.

Possibly no subject is much more questionable within the diet world nowadays than fats. Whilst in the 1970s and 1980s doctors attacked the quantity of fat in Americans’ diets, that appears to possess passed. Nowadays, the fights are gone the kind of fat that’s considered acceptable.

The majority of our fat originates from two primary sources. The very first is fatty foods. Usually solid at 70 degrees, they’re in steak, milk products and partially in chicken. The second reason is unsaturated fats, usually softer and much more liquid at 70 degrees. They’re in fish, nuts and vegetable oils. Many doctors and nutritionists still argue, quite strongly, the answer to health would be to highlight the unsaturated fats. Others believe that’s misguided.

This week’s news found us using a randomized controlled trial, which I’ve contended frequently is the greatest type of study to find out how one factor causes another.

The Minnesota Coronary Experiment would be a well-designed study which was conducted in a single elderly care and 6 condition mental hospitals from 1968 to 1973. Greater than 9,400 women and men, ages 20 to 97, participated. Data on serum cholesterol were on greater than 2,300 participants who have been around the study diets for over a year.

At baseline, participants were getting about 18.five percent of the calories from saturated fats, contributing to 3.8 percent from unsaturated fats. The intervention diet was considered a far more “heart healthy” one. It encouraged a decrease in the quantity of calories from fatty foods (like animal fats and butter) and much more from unsaturated fats, particularly linoleic acids (like corn oil). The intervention diet decreased the percent of calories from fatty foods to 9.2 percent, and elevated the percent from unsaturated fats to 13.2 percent.

The typical follow-up of these participants only agreed to be under 3 years. For the reason that time, the entire serum cholesterol dropped considerably more in individuals around the intervention diet (-31.2 mg/dL) compared to individuals around the control diet (-5 mg/dL).

There is, however, no decreased chance of dying. Contrary, there appeared to become an elevated mortality rate in individuals around the “heart healthy” diet, particularly among individuals 65 many older. More concerning, individuals who’d the higher decrease in serum cholesterol were built with a greater rate of dying. A 30mg/dL reduction in serum cholesterol was connected having a 22 percent rise in the chance of dying from the cause, despite modifying for baseline cholesterol, age, sex, adherence towards the diet, weight and bloodstream pressure.

Obviously, this is just one study. It involved only institutionalized patients. No more than one fourth from the participants adopted the diet plan for over a year. The diets don’t always seem like what individuals really ate, then or now. However this continues to be a sizable, randomized controlled trial, and it is difficult to imagine we wouldn’t a minimum of discuss it broadly.

Furthermore, they conducted a meta-analysis of studies that checked out this. Examined together, they still discovered that more and more people died around the linoleic-acidity-wealthy diets, even though the outcome was not statistically significant. Even just in a sensitivity analysis, which incorporated more studies, no mortality benefit might be found having a diet reduced fatty foods.

It’s worth noting that other meta-analyses both support and dispute this. A 2010 study contended that substituting unsaturated fats for fatty foods would cut back the rates of heart disease. So did a 2015 Cochrane review. A 2014 study in Annals of Internal Medicine, though, demonstrated the alternative.

People’s reactions for this news happen to be almost as much ast you’d expect. Supporters of the diet lower in saturated fats have known as the brand new study an “interesting historic footnote which has no relevance to current nutritional recommendations.” Others have stated when these studies have been printed once the study was over, “it may have altered the trajectory of diet-heart research and suggestions.Inches

This isn’t the very first time that data from lengthy ago have run against current recommendations. In 2013, an analysis was printed of retrieved data in the Sydney Diet Heart Study, a randomized controlled trial of the similar nature performed in males having a recent cardiac arrest or angina. Even though the study ended from 1966 to 1973, results weren’t available openly until 3 years ago. It, too, discovered that an eating plan greater in unsaturated fats brought to some greater rate of dying from cardiovascular disease.

Why wasn’t these studies printed decades ago? It’s entirely possible that modern computer systems enables us to complete analyses that couldn’t be practiced then. It’s entirely possible that researchers attempted, but were not able to obtain the results printed.

But it is also entirely possible that these outcome was marginalized simply because they didn’t match that which was regarded as “truth” at that time. The 2 principal investigators around the Minnesota study were Ivan Frantz and Ancel Keys, the second who could be the most influential researcher to promote saturated fats because the enemy of heart health. (Mr. Keys died in 2004.)

I am not suggesting anything sinister. I know that these two scientists absolutely thought that their prior epidemiologic work revealed that diets reduced saturated fats brought to reduce cholesterol levels and health. Research consistently confirmed the previous. When that lower cholesterol levels didn’t result in actual outcomes like lower mortality, though, they have to happen to be baffled.

Like others today, they’ve already had the ability to rationalize the end result away and choose it “has no relevance.” Regrettably, other, similar controlled trials appear to aid the concept the situation against saturated fats isn’t as robust as numerous think.

All of us must stress about publication bias, which takes place when outcomes of printed research is systematically not the same as outcomes of unpublished studies. Studies have proven that studies with statistically significant results are more inclined to be printed than individuals without. Studies having a low-priority subject or finding may be not as likely to become printed.

A primary reason that epidemiologic evidence frequently leads us to conclusions that can’t be supported is probably publication bias. Studies that find significant associations between foods (like meat) and frightening findings (like cancer) are more inclined to be printed than individuals that do not find individuals associations. When controlled trials are finally done, though, the frightening results frequently can’t be replicated.

But the most typical reason research isn’t printed happens because researchers don’t write up and send it in. That may be simply because they think it will not be recognized. It may be simply because they don’t believe the outcomes. Within the billed atmosphere of diet research, when people’s careers are made on certain ideas, it’s not to imagine our biases sneaking into play.

Regrettably, the healthiness of Americans yet others is on the line. Don’t let eat more polyunsaturated fats? Don’t let be staying away from fatty foods? The candid response is: I do not know. Given my overview of evidence, I uphold these recommendations, which basically focus more about foods and fewer on nutrients. I believe the condition of diet research generally is shockingly problematic.

It’s with enough contentration to talk about the information we are able to see. Knowing there’s most likely data available that individuals haven’t shared makes everything much, more difficult.